- Main article: List of The Big Bang Theory characters
- Sheldon Cooper, Ph.D., portrayed by Jim Parsons, is a theoretical physicist. Originally from Galveston, East Texas, he was a child prodigy, starting college at the age of 11, right after completing the fifth grade and received his first Ph.D. at 16. He has an IQ of 187 and an adherence to routine; a lack of understanding of irony, sarcasm, and humor; and a complete lack of humility or basic empathy. He is currently dating Amy Farrah Fowler and considers her to be his "girlfriend" instead of his previous designation of her being "a girl, and a friend, but not his girlfriend".
- Leonard Hofstadter Ph.D., portrayed by Johnny Galecki, is an experimental physicist with an IQ of 173 who received his Ph.D when he was 24 years old. He shares an apartment with colleague and friend, Sheldon Cooper. He and Penny dated at one point during the series, but they have since broken up. He dated Raj's sister, Priya for half of the fourth season, and a short period of the fifth season. He and Penny got back together in The Beta Test Initiation, although the relationship will be treated like a Beta Test, where bug reports will be presented when necessary.
- Penny, portrayed by Kaley Cuoco, is the attractive, blonde neighbor who lives across the hall from Sheldon and Leonard. Penny is from Omaha, Nebraska. She has aspirations to a career in show business, and has been to casting calls and auditions but has not been successful thus far. To pay the bills, she works as a waitress at The Cheesecake Factory. Her last name has never been revealed. She and Leonard dated throughout most of Season 3, but they have since broken up. In The Beta Test Initiation, she and Leonard got back together, although this time around, they are taking their relationship slowly, and treating it like a Beta Test and present each other bug reports when necessary.
- Howard Wolowitz, M.Eng., portrayed by Simon Helberg, works as an aerospace engineer. He is Jewish, and lives with his mother. Unlike Sheldon, Leonard, and Raj, Howard lacks a Ph.D. He defends this by pointing out that he has a master's degree in Engineering from MIT and the apparatus he designs are actually built and launched into space, unlike the purely abstract work of his friends. He provides outrageous pick-up lines and fancies himself a ladies man with suitably unimpressed reactions from Penny. Though he finds that he has limited success with other women at first, he begins dating Bernadette in season 3, but they break up; they get back together in the Season 4 episode The Hot Troll Deviation, become engaged in the episode The Herb Garden Germination, and married on the final episode of season 5, The Countdown Reflection.
- Rajesh Koothrappali, Ph.D., portrayed by Kunal Nayyar, originally comes from New Delhi, India. He is an astrophysicist. Known commonly as "Raj", he works alongside Sheldon exploring the string theory implications of gamma rays from dark matter annihilations. He is very shy around women and is physically unable to talk to them unless he drinks alcohol. However, he has much better luck with women as opposed to his overly confident best friend Howard. His sister, Priya, dated Leonard.
- Bernadette Rostenkowski Wolowitz, Ph.D., portrayed by Melissa Rauch, is a former waitress and co-worker of Penny paying her way through graduate school microbiology studies. Bernadette is introduced to Howard by Penny. At first she and Howard did not get along, as they appeared to have nothing in common. When they found out that they both have overbearing mothers, they feel a connection. She was upgraded to main cast status in the episode The Hot Troll Deviation, in which she and Howard revisit their previously unsuccessful relationship. They got engaged in Season 4's The Herb Garden Germination and married on the final episode of season 5, The Countdown Reflection. Since earning her doctorate, Bernadette is now finally a microbiologist, and earns more than her husband, Howard.
- Amy Farrah Fowler, Ph.D., portrayed by Mayim Bialik, is a woman Raj and Howard met on an online dating site using a faux account for Sheldon. She is essentially the female duplicate of Sheldon and she and Sheldon become friends although, as Sheldon claims, she is a girl and is his friend, but she is not his girlfriend. However, since the tenth episode, she is officially Sheldon's girlfriend. Amy is a neurobiologist and is more inclined to explore human relationships than Sheldon partly due to Penny's friendship. Amy is from Glendale.
|Episode (Series)||Episode (Season)||Title||Original Air Date||Directed By||Description|
|88||1||The Skank Reflex Analysis||September 22, 2011||Mark Cendrowski||
Penny is worried with how damaged her friendship with the guys will be in the aftermath of her sleeping with Raj while Sheldon becomes the leader of the paintball team.
|89||2||The Infestation Hypothesis||
September 22, 2011
A fight between Sheldon and Penny leaves Amy caught in the middle, while Leonard tries to spice up his long-distance relationship with Priya.
|90||3||The Pulled Groin Extrapolation||
September 29, 2011
Leonard accompanies Amy to a wedding. Meanwhile, Howard and Bernadette spend a weekend with Mrs. Wolowitz.
|91||4||The Wiggly Finger Catalyst||October 6, 2011||Mark Cendrowski||Penny finds the perfect girl for Raj to date. Meanwhile, Sheldon uses Dungeons & Dragons dice to make life's trivial decisions.|
|92||5||The Russian Rocket Reaction||October 13, 2011||Mark Cendrowski||Sheldon and Leonard get invited to a party at Wil Wheaton's house, and Howard gets an out-of-this-world opportunity.|
|93||6||The Rhinitis Revelation||October 20, 2011||Mark Cendrowski||Sheldon competes with the gang for his mother's affection when she comes to visit.|
|94||7||The Good Guy Fluctuation||October 27, 2011||Mark Cendrowski||A cute comic book artist puts Leonard and Priya’s relationship to the test, while Sheldon tries to scare the guys for Halloween.|
|95||8||The Isolation Permutation||November 3, 2011||Mark Cendrowski||Amy becomes heartbroken when she discovers that Penny and Bernadette went wedding dress shopping without her.|
|9||The Ornithophobia Diffusion||November 10, 2011||Mark Cendrowski||
Sheldon tries to cure his phobia of birds, while Leonard and Penny experiment with hanging out alone.
|97||10||The Flaming Spittoon Acquisition||November 17, 2011||Mark Cendrowski||
When Stuart, from the comic store, asks Amy out on a date, Sheldon becomes jealous and acts on their relationship.
|11||The Speckerman Recurrence||December 8, 2011||Anthony Rich||
Leonard confronts his fears when he is contacted by a bully who tormented him in high school.
|99||12||The Shiny Trinket Maneuver||January 12, 2012||Mark Cendrowski||Howard and Bernadette deal with the possibility of ever having a child, while Sheldon and Amy encounter the first bump in their relationship.|
|100||13||January 19, 2012||Mark Cendrowski||Leonard decides to invite Penny out on a dinner date, hoping to rekindle their relationship.|
|101||14||The Beta Test Initiation||January 26, 2012||Mark Cendrowski||Leonard and Penny deal with the possibility of a reconciliation and Raj finally finds a "woman" that he can talk to without being drunk; the Siri in his new iPhone. Meanwhile, Amy helps Sheldon start a new YouTube series called "Sheldon Cooper presents Fun with Flags".|
|102||15||The Friendship Contraction||February 2, 2012||Mark Cendrowski||Tired of being more like Sheldon's chauffeur than his roommate, Leonard invokes Clause 209 of The Roommate Agreement that allows him to be only an acquaintance. Meanwhile, Howard has been chosen to join NASA's next mission to space and tries to get a neat nickname.|
|103||16||The Vacation Solution||February 9, 2012||Mark Cendrowski||
Forced to undergo his mandatory vacation by President Siebert, Sheldon decides to join Amy at her laboratory, only to find himself struggling to do things right. Meanwhile, Bernadette and Howard face the issue of signing a prenuptial agreement, at her father's insistence.
|104||17||The Rothman Disintegration||February 16, 2012||Mark Cendrowski||Sheldon and Kripke engage in sporting activities to battle each other out in order to find the winner of who will get the newly vacated Professor Rothman's office. Meanwhile, Penny feels uncomfortable with Amy's latest friendship gift.|
|105||18||The Werewolf Transformation||February 23, 2012||Mark Cendrowski||Sheldon's world turns upside-down when his barber gets sick. Meanwhile, astronaut training gets Howard to rethink his decision to join the upcoming mission to space.|
|106||19||The Weekend Vortex||March 8, 2012||Mark Cendrowski||Sheldon plans a marathon video game event for the gang the same weekend Amy wants him to go to her aunt's birthday party.|
|107||20||The Transporter Malfunction||March 29, 2012||
Sheldon opens his mint-condition vintage Star Trek transporter -- a gift from Penny which he ends up breaking. Meanwhile, Raj asks his parents to set him up with someone.
|108||21||The Hawking Excitation||April 5, 2012||Mark Cendrowski||When Howard gets the opportunity to work with Stephen Hawking, Sheldon will do whatever it takes to meet him, even if it means turning up to work in a french maid costume.|
|109||22||The Stag Convergence||April 26, 2012||Peter Chakos||The guys organize a bachelor's party for Howard, which leads to the unraveling of Howard's secrets. Bernadette accidentally hears about them, threatening their impending nuptial.|
|110||23||The Launch Acceleration||May 3, 2012||Mark Cendrowski||Howard's launch date gets pushed up, coinciding on the same week as his wedding, putting him in a dilemma. Leonard endangers his relationship with Penny with a sudden proposal to her, and Sheldon finds himself developing feelings for Amy after a few gestures from her.|
|111||24||The Countdown Reflection||May 10, 2012||Mark Cendrowski||
Howard and Bernadette decide to elope after their wedding is put on hold so Howard can join NASA's mission to the International Space Station (ISS). The gang rush to organize the wedding ceremony and get themselves ordained as ministers. Howard heads to the ISS.