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Dr. Leonard Leakey[2] Hofstadter (Johnny Galecki) is an experimental physicist with an IQ of 173 who is originally from New Jersey and received his PhD at age 24, spending at least some of his time at Princeton University. He shares an apartment in Pasadena with colleague and friend Dr. Sheldon Cooper. Unlike his equally geeky friends, Leonard is interested and quite adept in building interpersonal and social relationships with others. Compared to his friends he is relatively successful with women. The writers have toyed with a romance between him and next-door neighbor Penny since the pilot, with their unresolved sexual tension being a major force for drama. Leonard dated Penny for most of Season 3, although they had dated briefly at the end of Season 1. Aside from Penny, Leonard has had romantic relationships with coworker Leslie Winkle, physician Stephanie Barnett, an unnamed French literature PhD, and North Korean spy Joyce Kim. Following his breakup with Penny, Leonard began a relationship with Raj's sister Priya in Season 4, and it is implied they had a brief sexual encounter before the start of the series on an occasion when Priya visited Raj. The two attempted a long-distance relationship after Priya moved back to India, but Leonard eventually broke up with her in Season 5 after she admitted to cheating on him with her former boyfriend. In Season 5's "The Beta Test Initiation", Leonard and Penny start dating anew though their relationship is rocky. Over the next two years they talk of marriage and each have unsuccessful proposals until the end of season seven when they become engaged. Leonard's family includes other accomplished scientists: his mother, Dr. Beverly Hofstadter, is a world-renowned psychiatrist, his sister is a biologist and his father an anthropologist. Also, his brother Michael is a Harvard law professor. It is mentioned in the season 2 episode "The Maternal Capacitance" that Leonard is the least successful member of his family. He is also known to be lactose intolerant and cannot process corn, as Sheldon states in "Pilot". Leonard also plays the cello. The cause of the elevator not working is also due in part to Leonard (and Sheldon) as the experimental rocket fuel he was developing was improperly mixed within their apartment and Sheldon threw the canister into the elevator shaft right before the explosion.

Dr. Sheldon Lee Cooper (Jim Parsons) is a theoretical physicist, possessing a Bachelor of Science, Master of Science, PhD, an ScD, and an IQ of 187. Originally from East Texas, he was a child prodigy, starting college at the age of 11, and receiving his PhD at age 16. He is cold and calculating, and refrains from any form of physical contact if possible. Sheldon exhibits a strict adherence to routine to the point of exhibiting obsessive–compulsive personality disorder, performing specific activities on specific days and specific times, such as doing the laundry on Saturday night at 8:15. Any disruption to this routine distresses him enormously. A running gag has him always knocking on doors or other surfaces in a pattern of three knocks and one call repeated three times, which he has to complete no matter what. He has forced Leonard into signing an absurdly exhaustive "Roommate Agreement", and later enters a similar "Relationship Agreement" with Amy Farrah Fowler. Sheldon has great difficulty identifying sarcasm and irony and responding in kind, and a recurring topic is his efforts to acquire these skills. He has also enormous difficulties lying or even keeping a secret, giving himself away with wild facial tics and implausible statements. He is however fond of occasionally playing a prank, which he typically punctuates with his trademark exclamation "Bazinga!". Sheldon has a superiority complex and makes no effort to hide his contempt for other people's intellects, often making highly inappropriate comments. A common joke is his inability to drive, although he did receive a learner's permit.[3] Sheldon loves comic books and science fiction like his friends, but to the point of being obsessed about them, and is a fan of Spock, a fictional character of the Star Trek franchise.[4] Unlike Leonard and Raj who come from intellectual families, Sheldon stands out from his own relatives. His father, George, whose death pre-dates the series, was described as a stereotypical Texan who liked football, skeet shooting, and heavy drinking,[5][6] his mother, Mary, is a devout Evangelical Christian, who does not possess anything near Sheldon's intellect (though she displays a great deal of common sense);[7] his twin sister, Missy, and as-yet unseen brother, George Jr., were both described by Mary as being "dumb as soup". His fraternal twin sister who later has a baby boy makes Sheldon an uncle. He meets Amy Farrah Fowler in the Season 3 finale and starts a highly unusual and very slowly evolving relationship with her and by season 7 they having started kissing each other. Previous to this, he has also exhibited some affinities with Leonard's equally unemotional mother.

Penny (surname has not yet been revealed) (Kaley Cuoco), is Leonard and Sheldon's neighbor across the hallway. Originally from a small town outside Omaha, Nebraska, she was a waitress and occasional bartender at the local Cheesecake Factory until season 7 and is an aspiring actress. Her educational qualifications (she had dropped out of community college) are a constant source of disparaging comments from Sheldon. She has dated several men during the course of the series, including Kurt, Stuart, and Zack, but her recurring romantic interest is Leonard. Leonard pursued Penny during season 1; they dated briefly at the start of season 2 which led to some awkwardness; they began dating again and were a couple for most of season 3, but she broke up with him after he told Penny he loved her and she was not ready to reciprocate. Penny and Leonard begin to date again "slowly" during the fifth season, though he does upset her by impulsively asking her to marry him during intercourse at the end of season five. After several unsuccessful proposals from both sides, Penny realizes that her happiness is derived from her relationship with Leonard and they become engaged. She has a tense relationship with Sheldon, whose nerdy and obstinate personality often exasperates her, but they are ultimately good friends, helping each other out in various situations. By season four, Penny also begins to socialize more with Bernadette and Amy, who frequently hang out in Penny's apartment, go out together and comfort each other. Bernadette and Amy are both shown to be simultaneously envious of and threatened by Penny's more outgoing personality. Not much is known about Penny's family, but it is mentioned in the series that her father, Wyatt (portrayed by Keith Carradine[8]), raised her like a boy, her mother smoked marijuana while she was pregnant with her, her sister shot her husband while they were intoxicated and her brother is a meth dealer. Cuoco began being credited as Kaley Cuoco-Sweeting, starting with the season seven episode, "The Convention Conundrum".

Howard Joel[9] Wolowitz (Simon Helberg) is an aerospace engineer at Caltech's Department of Applied Physics with a Masters in Engineering who often hangs out at Leonard and Sheldon's apartment. Unlike Sheldon, Leonard, and Raj, Howard has no doctorate, and often gets disparaged as a result, especially by Sheldon. He defends this by pointing out that he has a master's degree in Engineering from MIT and that the equipment he designs is launched into space, unlike the theoretical work of his friends. In the season 5 finale, Howard goes to the International Space Station on Expedition 31. Howard lives in Altadena with his domineering, belittling and unseen mother who treats him like a child. While he sometimes expresses irritation at this treatment, for the most part he appears to prefer it.[episode needed] Howard dotes on his mother and participates in many of her daily routines. A recurring gimmick in the series is Howard and his mother communicating with each other from different rooms by yelling, a habit which Bernadette also adopts in later episodes. His father left them when he was eleven, and Howard gets visibly distressed when the subject comes up. Howard fancies himself a ladies' man and attempts pick-up lines whenever a woman is present, which often come off as inappropriate and disgusting, although he has dropped this habit since he started going out with Bernadette.[episode needed] He is Jewish, but he is not very serious about his faith, and does not keep kosher. For example, when the group's favorite Chinese restaurant raised the price of pork, Howard remarked, "It's getting tougher and tougher to be a bad Jew." However, he does observe Sabbath and the Jewish holidays. In the pilot episode, it is shown that he is a polyglot and can speak English, French, Mandarin, Russian, Arabic, and Farsi, along with fictional languages like Klingon and Sindarin. He is asthmatic, allergic to peanuts, almonds, and walnuts, prone to canker sores and pink eye, succumbs to seasickness, has an incredibly high genetic risk of heart illness, and has transient idiopathic arrhythmia. In Season 5 episode 4, it is shown that he knows American Sign Language. Howard dated Bernadette briefly in season 3. After some difficulties, they resumed their relationship in season 4, which culminated in their engagement. In the season 5 finale, Howard and Bernadette are married on the roof of the apartment building shortly before he has to leave for Kazakhstan where he is to be sent to the International Space Station. In season 6, he finally leaves his mother's house and moves into Bernadette apartment.

Dr. Rajesh Ramayan[4][11] "Raj" Koothrappali (Kunal Nayyar) is Howard Wolowitz's best friend, and yet another genius of the group; his name is usually shortened to "Raj". He is originally from New Delhi, India, and he works in the Physics department at Caltech, where his area of expertise is particle astrophysics. He lives in an apartment in Pasadena. As with his friends, he is mutually involved with and obsessed with science fiction and comic books in general, and is usually the one to propose various real-life questions derived from such works, such as the functions of the tails of the Na'vi in the film Avatar. He is also a fan of Harry Potter. Raj dislikes India, Indian food, and Indian music, he also appreciates the Indian lullabies his mother sang to him and the catchiness of Hindi phrases. Raj is a Hindu and believes in karma (reincarnation), but eats beef. Raj is very shy around women, and finds himself unable to speak to or while in the presence of them unless he drinks alcoholic beverages, or he believes he has done so.[12] When Penny or Bernadette is around, Raj usually whispers what he wants to say to Howard or Leonard, who then repeats or responds to what Raj says out loud, although at times Howard will embarrass him by saying something completely different and inappropriate.[13] Despite this, Raj has sometimes ended up in bed with women, leaving the other guys perplexed.[14] Unlike his friends however, Raj has many quite feminine interests such as reading Archie Comics and Twilight and watching chick flicks such as Bridget Jones's Diary. A recurring joke in the series has people, including his parents and Leonard's mother, speculating that Raj might be gay due to his feminine interests and his close friendship with Howard, with whom he has arguments similar to those of a married couple. However, Raj has always stated that he is straight, but metrosexual. He has had an infatuation with Penny, and secretly wrote love poems about Bernadette. Raj comes from a very wealthy family in India, and often communicates with his parents, Dr. and Mrs. Koothrappali, via webcam.[12] He has a younger sister, Priya, who is mentioned to have dated Leonard briefly before the series timeline began and dates him again in Season 4, breaking up with him in Season 5. After making a brave speech about not being embarrassed to be single, Raj started seeing a shy and sweet woman named Lucy. Lucy has many things in common with Raj including her fear of being in large crowds. In the season 6 finale, Raj finds he can now talk to women without alcohol, however he never stops talking. In season 7, Raj begins to interact with women ending the season with a red-headed girlfriend named Emily