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Two brilliant ("a combined IQ of 360") young physicists, Leonard and Sheldon, are the kind of "beautiful minds" that understand how the universe works. But their PhDs don't help them interact with people, especially women. All this begins to change when a free-spirited newly single beauty named Penny moves in next door. When Leonard and Sheldon meet Penny, Leonard is immediately interested in her (saying their babies will be smart and beautiful), but Sheldon feels his friend is chasing a dream he'll never catch (adding 'and imaginary'). Sheldon is quite content spending his nights playing Klingon Boggle with their socially dysfunctional friends, fellow geeky Caltech geniuses Wolowitz (a wannabe ladies man) and Koothrappali (who is so shy he can not speak to attractive women). However, Leonard sees in Penny a whole new universe of possibilities... including love. Leonard is so infatuated with Penny that after letting her use their shower (hers was broken) he agrees to try and retrieve her TV from her ex boyfriend, Kurt's, place. However the boyfriend depants both Sheldon and Leonard and they are unable to retrieve the TV. Feeling bad Penny offers to buy them and their friends dinner.
Sheldon and Leonard go over to Penny's apartment to drop off a package that came for her. Sheldon is deeply disturbed when he sees how messy and disorganized her apartment appears. Later that night, when Leonard is sleeping, Sheldon sneaks into Penny's apartment to clean and organize it. Leonard catches him and tries to stop him, but Sheldon is obsessed. Penny wakes up and yells at them, prompting Leonard to ask how she knew (Sheldon had left an organizational diagram for her closet). Sheldon goes to apologize but Penny can not believe his attitude and remains upset. Later on Leonard goes to apologize, prompting Penny to hug him and say 'we're okay'. Leonard volunteers to sign for a package in an attempt to make a good impression on Penny, but when he enlists Sheldon for help, his attempt at chivalry goes terribly awry.
On the date Penny mentions the man Leonard had seen was not her boyfriend, and that she has a habit of having weekend long flings to get over relationships. Excited, Leonard begins to become more confident but after accidentally hurting himself the date becomes a disaster and Penny takes him home. Leonard does not get the courage to reveal his true feelings to Penny, even though she had suspected what he was up to. Leonard asks a woman out after he finds out that Penny is seeing someone.
Sheldon is fired from his job as a physicist at the university when he insults his (in his opinion) less-gifted new boss Dr. Eric Gablehauser (Mark Harelik). His change of circumstance sends him into a downward spiral of depression in which Leonard tries to cure by sending for Sheldon's mom (Laurie Metcalf). When she arrives for a visit, the boys realize she is completely the opposite from what they expected. She is down-to-earth, sweet, and a devout Christian ("All that science stuff that comes from Jesus"). After waiting it out his mother finally forces Sheldon to apologize and he is given his job back, after she flirts with Dr. Gablehauser (she is apparently widowed). Sheldon asks if Dr. Gablehauser will be his new Daddy and his mother replies, "We'll see..." Sheldon's getting fired forces him to explore what life has to offer outside physics, leaving Leonard to take drastic action to snap his friend out of his funk.
When Sheldon comes home and finds a necktie on Leonard's door, he runs to Penny’s apartment to ask her what the necktie means. Penny tells him and seems slightly disappointed, though she does congratulate Leonard later on. Leonard tries to figure out what her words meant but eventually gives up, deciding he should choose a real relationship (Leslie) over an imaginary one (Penny). However when he arrives in the lab Leslie makes it clear she used him just to satisfy her sex drive, saying she's 'Good till New Year's'. Leonard later tells Penny, who walks away with a smile on her face; she seems to be quite happy to hear this news. Fearing he's wasting his time on Penny, Leonard ends up making a connection with Leslie.
The guys are invited to Penny's Halloween party, first turning it down as they 'don't dance' but changing their mind when costumes are mentioned. Once at the party only Wolowitz and Leonard attempt to socialize; with mixed success. Penny's ex-boyfriend Kurt shows up and humiliates Leonard, causing him to leave. Penny goes to check on him and apologizes. Both drunk and upset she kisses Leonard, which he refutes with the obvious reasons as to why she's doing it. Penny says he's sweet and wonders why more men can't be like him, with Leonard replying, "Because the human race wouldn`t survive". Penny goes to leave and kisses him once more in the doorway. Meanwhile, Wolowitz can not find Koothrappali, who ends up going home and has sex with a girl he had met at the party, who found him to be a 'good listener' (as Koothrappali is so shy he can not speak to attractive women). Penny hosts a Halloween party, putting Leonard, Sheldon, Wolowitz, and Koothrappali through a new test of their social skills.
Penny's slutty 'friend' Chrissy (Brooke D'Orsay) from Nebraska is in town, and ends up being seduced by Wolowitz. The pair take over her apartment causing her to sleep on Leonard and Sheldon's couch for the night. With Wolowitz gone Penny takes his place on their Halo team, causing Sheldon much distress as she is naturally good at it. Chrissy moves in with Wolowitz (and his mother) taking up all his time. Sheldon is distraught over the odd number in the group believing they can no longer function. He's even more distraught when he relents and lets Penny join in on Halo night, but she declines the offer to instead go dancing with her friend. Believing they are falling apart as a group, the guys go to speak to Wolowitz. When they arrive they hear Chrissy and Wolowitz's mother arguing loudly, causing Chrissy to leave. Wolowitz, once again single, says 'So, Halo night?' and the group is restored. With Wolowitz AWOL with one of her friends, Penny's recruited to fill in for him on the guys' Halo team.
Koothrappali is overwhelmed after his parents arrange a blind date with a girl from his childhood, as he can not talk to attractive members of the opposite sex. Penny takes up bar tending for some extra money; and as she practices mixing drinks with the guys they discover that after a few drinks Koothrappali can actually talk to women. However on his date at Penny's restaurant (with all the guys watching from the bar), he becomes obnoxious, and the girl ends up leaving with Sheldon after he accidentally complimented her by comparing her to a beautiful Indian fairytale princess. Koothrappali and Leonard return to Leonard's apartment where Koothrappli tries to explain to his parents what happened. Even though he is already upset things become worse when his parents find out he was drinking and he gets lectured and has to leave the apartment. Sheldon returns and Leonard asks him what happened after the pair had left the bar. Sheldon seems to not have thought of it as a date, implying he will not see her again (making Leonard wonder out loud, "I wonder who will tell his parents they're not getting grandchildren"). Raj's parents set him up on a blind date, and when he discovers he can talk to her, she shows interest in Sheldon.
Cleaning up after an internet experiment Leonard discovers a letter in the trash can. He and Sheldon had been invited to present some research they had done together at a physics conference. However Sheldon does not believe in such things and says if he won't go no one can. Leonard defies him and says he will go and present the findings on his own. This causes a rift between the two which Penny tries to mend but accidentally makes worse. At the conference Sheldon appears and has a physical altercation with Leonard. In the end, the fight is captured by Wolowitz and put on Youtube.
Penny was given a part in Rent, though after hearing her sing "Out Tonight" extremely off-key ("What the hell is that?" "I don't know, but if cats could sing...they'd hate it too). Leonard lies to avoid seeing her performance so he won't hurt her feelings. Sheldon becomes paranoid that Leonard's lie was 'too transparent' and eventually creates an intricate lie about his non-existent drug addicted cousin Leo (DJ Qualls), who was in need of an intervention (and thus why they could not see the play). Sheldon becomes so obsessed he actually has a fellow physcist (who double majored in theatre) play the cousin to convince Penny that the lie is true. In the end Leonard still has to see the tape of Penny's performance, thus the lie did him no good at all.
Penny returns from visiting family in Nebraska, and as she picks up her mail from Leonard she mentions it was a bad trip because 'everyone got sick'. Sheldon freaks out as according to Leonard 'he's a bit of a germaphobe'. Sure enough Sheldon becomes sick and instantly becomes the biggest pain possible. Leonard and the guys hide from him at a Planet of the Apes marathon, leaving Penny unwillingly to take care of Sheldon. However Leonard accidentally breaks his glasses and must re-enter the apartment, where Penny catches him and sticks him with Sheldon. In the end both Leonard and Sheldon are sitting sick and injured on the couch. Sheldon wonders if Penny will come take care of them, to which Leonard replies, "I don't think Penny is ever coming here again."
Sheldon is overcome with I.Q. envy when he meets a smarter 15-year-old science prodigy named Dennis Kim (Austin Lee). Losing faith in his own research, he annoys his circle of friends and colleagues by criticizing their work (prompting them to say "Go away!" whenever he's around). Deciding his work in physics is useless he decides to aim for the Nobel Peace Prize by creating a 'Nuevo Jerusalem' for the Jewish people in the Mexican desert (thus creating peace in the Middle East). The guys, tired of his insults and his craziness decide to take Dennis out of the picture by getting him distracted with girls. At his welcome party their plan works (though mostly by accident) and Dennis leaves with a blonde 15 year old (Unfabulous's Emma Degerstedt) for the mall. Excited, Sheldon declares his work will continue on and 'human relationships will continue to baffle and repulse me'. The guys were excited Sheldon was back to his old self, but Leonard, Wolowitz and Rajesh were upset and perplexed at how Dennis was able to get girls yet they were not.
The guys decided to compete in a physics bowl but find Sheldon's showboating too much and kick him off the team, telling him "You're annoying and no one wants to play with you anymore". Upset, Sheldon vows to form his own team and compete against them. The guys in need of a 4th member ask Leslie Winkle to join them. After being told it is to defeat Sheldon she joins as Sheldon had once told her that she should give up her research to bear children and do laundry.
Leonard buys a replica time machine online believing it to be a miniature... though it turns out to be full-sized. As the boys move it into the apartment they accidentally make Penny late for work causing her to lash out at Leonard for his nerdy ways. Upset, Leonard decides to get rid of all his 'nerdmabelia' and the guys try to convince him not to (or sell it to them, whichever). In the end Sheldon confronts Penny about her own love of childish things (Hello Kitty, Beanie Babies, etc) and she apologizes to Leonard. However she has a new boyfriend named Mike, and once Leonard finds this out he reverts to his old ways.
Sheldon's sexy twin sister arrives in town from Texas, and all of Sheldon's friends fight over who will get to be with her.
When the boys dine at Penny's restaurant she learns Leonard has never had a birthday party, as his parents didn't believe in celebrating anything but achievements. She decides to throw him a surprise party, and blackmails Sheldon to join her. However when the day of the party arrives she finds Sheldon did not buy a birthday gift. After some help from Wolowitz in convincing him it was a 'non-optional social convention' Penny drives Sheldon to a computer store where he becomes distracted, helping other customers with their tech-related questions. Meanwhile Wolowitz is in charge of keeping Leonard busy until the party. After pretending to eat a peanut bar (to which he is allergic) Leonard drives him to the emergency room. Due to Sheldon's absent-mindedness, Wolowitz has to keep Leonard distracted even longer, and after a promise from Penny of "being shown which of her friends is easy" Wolowitz actually eats the peanut bar...causing him to swell up in an allergic reaction. After being at the hospital for several hours (in which they tested everything for fear of being sued) Wolowitz and Leonard arrive back at the apartment to find Penny asleep on the couch, Sheldon asleep in the chair, and Koothrappali drunk singing karaoke telling them everyone left an hour ago. In the end Penny shows Leonard a cell phone video of the party and ends up giving him a kiss.
Penny breaks up with her boyfriend after he posted intimate details about her on his blog. Leonard goes to comfort her and in doing so accidentally convinces her to get back with her boyfriend. As Leonard laments the situation to the guys, Penny returns and screams at Leonard, saying he made things worse. He tries again and she apologizes; saying it wasn't his fault: she explains that when she went over to make up, she found her boyfriend had already moved on. As Penny laments her choices in men Leonard awkwardly asks her on a real date. Penny thinks for a moment and agrees saying, "Sure, why not?". A few days pass and both Leonard and Penny are worried that this date will ruin their friendship. They both seek Sheldon's advice. Sheldon advises Penny that “just like Schrödinger's cat being alive or dead at same time” her date with Leonard currently has both “good and bad” possible outcomes. The only way to find out is to “open the box”, or in other words to go on the date and find which outcome it is. Leonard is also given the same advice, and understands it right away.
Penny and Leonard return from the restaurant while Howard and Rajesh spy on them, using a webcam on the corridor connected to a laptop. They try to convince Leonard that the date wasn't working well: they think that when Penny said "let us slow down a bit", it meant that the "fish is bad". But they are obviously envious. On the other hand, after Penny and Leonard's date, Penny feels uncomfortable having not gone to college. She is afraid that Leonard would become bored with her. She lied to Leonard about completing her own college and makes Sheldon keep her secret. This request to deceive Leonard is very hard for Sheldon (and his facial expressions) and results in a drastic decision on Sheldon's part.
The guys return from a Renaissance Fair and see Penny with a new guy, Eric (Travis Schuldt), prompting a jealous Leonard to pursue a relationship with fellow physicist Leslie Winkle. All the guys as well as Leslie humiliate Leonard for his apparent failure to keep Penny. Leslie eventually agrees to date Leonard who convinces Sheldon to leave the apartment, to give his roommate and Leslie some privacy. On the staircase, while playing Super Mario 64, Sheldon explains to Penny that he feels uncomfortable with Leonard dating his arch enemy, Leslie, who is a "sloppy, arrogant, sub-par scientist".
Sheldon becomes distracted from playing Age of Conan by Penny who has accidentally attempted to use her car keys to open her apartment door. Sheldon learns that Penny is frustrated by her failures in life specifically her not getting into any of the parts in plays she's tried out for, not having sex for six months, not receiving a raise at work and on her way up the stairs she swallowed a fly. Sheldon invites her into his apartment to wait until the locksmith arrives to open her door. Penny becomes curious about the game Sheldon is playing and quickly becomes addicted. They quickly try to help her regain her regular life back as they try to set her up with an online dating service which failed miserably. After falling deep into her addiction she inadvertently accepts an online date consisting of questing and drinking ale at the local virtual tavern with Howard. She quickly realizes what she's done and promptly stops playing the game.
When Sheldon "breaks up" with Amy, the guys worry when he starts replacing her with cats.
Wolowitz tries to get back together with Bernadette. Sheldon and Raj go to war at the university.
Leonard is depressed to realize all the other guys have girlfriends, while he doesn't. Amy wants to introduce Sheldon to her mother.
When Raj's sister has a one-day layover he forbids the others from hooking up with her, unaware she and Leonard already did long ago.
The rest of the gang is interviewed by the FBI for Wolowitz's security clearance, with Sheldon accidentally letting slip some damaging information.
The guys camp out in line to see a print of Raiders of the Lost Ark with 21 extra seconds and are outraged to see Wil Wheaton and his friends being allowed to skip the line. Penny and Bernadette invite Amy to their girls night.
When Penny's father visits, she gets Leonard to pretend to still be her boyfriend. Meanwhile, Howard, Raj, and Bernadette spend the night on an astronomy project.
Amy crushes on one of Penny's dim ex-boyfriends, Zack. Raj and Wolowitz argue over who'd be the better superhero.
The guys get Zack and Penny to join their Justice League costume for a New Year's Eve bash at the comic book store.
Their friendship becomes strained when Sheldon tries to take over Leonard's creation of a smartphone application that solves differential equations.
A science convention at a hotel leads to Bernadette running into an ex-boyfriend and Wolowitz worrying he can't quite compare.
Hoping it will make him a better teacher, Sheldon has Penny give him acting lessons. Raj has fantasies about Bernadette.
After meeting at a fundraising gala, an aged, but wealthy, Caltech donor makes Leonard ponder if he's willing to have sex with her to secure another donation.
Bernadette tells Howard that it's time to choose between moving in with her or staying with his mother. Leonard discovers Raj's sister Priya is back in town and reconnects with her, and Amy tries to comfort Penny when she finds out.
Told Leonard is the center of the gang and miffed that they've started hanging out at Raj's, Sheldon seeks to form a new group of friends of which he can be the center.
Sheldon is baffled by Wolowitz's magic trick. Meanwhile, Priya disapproves of Leonard continuing to be friends with Penny.
When Sheldon has his World of Warcraft account hacked and his character stolen from, the guys team up to discover out who did it. Meanwhile, Bernadette and Amy try to help Penny deal with Leonard's continuing relationship with Priya.
Sheldon and Amy decide to start rumors about themselves as a social test. Meanwhile, Howard takes his relationship with Bernadette to an even higher level.
Miffed over Priya breaking down the Roommate Agreement using legal theory, Sheldon joins Penny, Bernadette, and Amy on their girls' night.
Amy recognizes a dinner invitation to be a chance for Bernadette to spy on Leonard and Priya for Penny. Meanwhile, a lonely Raj considers taking experimental medication to cure himself of his inability to talk to women while sober, and Sheldon devises three-person chess.
Mrs. Wolowitz ends up in the hospital after Howard tells her he's marrying Bernadette. While there, Leonard stresses over Penny and Priya warming up to one another.
Hearing Star Trek sex games between Leonard and Priya sends Raj to live with Sheldon. Bernadette's earning her Ph.D makes the guys mock Wolowitz for not having one even more.
After spending the night with Raj, Penny is worried that her friendship with the guys is in jeopardy, while Sheldon becomes the paintball team leader.
Sheldon is aghast to learn the new chair in Penny's apartment was someone else's garbage. Leonard and Priya try a long-distance relationship.
Leonard escorts Amy to a wedding. Meanwhile, Howard convinces Bernadette to spend the weekend with him at his mother's house as a trial run, and Sheldon gets involved in model trains.
Penny finds the perfect girl for Raj to date. Meanwhile, Sheldon uses Dungeons & Dragons dice to make life's trivial decisions.
Sheldon is miffed that Leonard plans to attend a party hosted by his nemesis, Wil Wheaton. Meanwhile, Howard is offered a chance to be a payload specialist on the International Space Station.
When his mother comes for another visit, Sheldon is disappointed that she's stopped being the mother he wants her to be.
Leonard finds himself drawn towards a comely comic book illustrator. Meanwhile, Sheldon tries to scare the gang for Halloween.
When it is revealed that Penny and Bernadette went wedding dress shopping without her, Amy becomes heartbroken and pressures Sheldon for sex.
Sheldon tries to cure his phobia of birds, while Leonard and Penny go to a movie just as friends.
Sheldon finds himself jealous when Amy goes on a date with Stuart. The other guys can't resist the allure of the latest collectable card game expansion pack.
Leonard is hesitant when a bully from high school wants to meet for a drink. Meanwhile, Penny comes to realize she was a bully herself.
Sheldon finds himself in hot water when he doesn't appreciate Amy's recent accomplishment. Howard discovers Bernadette doesn't interact well with children.
Leonard asks Penny out on an impromptu romantic date.
Leonard and Penny create lists of 'bugs' in their relationship in an attempt to strengthen it. Meanwhile, Sheldon and Amy create a YouTube video series called Fun with Flags, and Raj develops an unhealthy attachment to Siri on his iPhone.
Leonard can't take Sheldon's continued selfishness and agrees to dissolve the Roommate Agreement. Howard wants to have a cool nickname for when he's an astronaut.
Forced to use his vacation time, Sheldon dabbles in biology in Amy's lab. Bernadette reveals to the girls that her father wants her to make Howard sign a pre-nup.
When a new office space is made available, Sheldon goes head to head with his nemesis, Kripke, for the right to move in. Meanwhile, Penny is unsettled by painting given to her by Amy.
Sheldon is forced into altering his precious schedule after his barber falls ill. Meanwhile, the training required to be an astronaut has Wolowitz wondering if he has the right stuff.
Sheldon incurs Amy's ire when he chooses a weekend of videogaming with the guys over a birthday party for her aunt.
Sheldon faces a crisis of conscience after breaking a Star Trek toy given to him by Penny. Meanwhile, a lonesome Raj is smitten after a date set up by his parents.
When Stephen Hawking visits Caltech to give a lecture, Sheldon goes to great lengths for a chance to meet his hero in person.
A bachelor party and his sexual past puts Howard's marriage to Bernadette in jeopardy.
Howard's space mission is moved up, conflicting with the wedding. Meanwhile, Leonard mentions something in the bedroom thatfreaks outPenny.
As Howard awaits blast-off, he recounts how the gang threw together a last-minute wedding for him and Bernadette.