Johnny Galecki as Leonard Hofstadter: An experimental physicist with an IQ of 173, who received his PhD when he was 24 years old. Leonard is a nerd who loves video games, comic books, and Dungeons & Dragons. Leonard is the straight man of the series, in which he shares an apartment in Pasadena, CA, with Sheldon. Leonard is smitten with his new neighbor Penny when they first meet, and they eventually marry.
Kunal Nayyar as Rajesh Koothrappali: A particle astrophysicist originally from New Delhi, India. Raj is initially unable to talk to women unless he drinks alcohol. Raj also has very feminine tastes and often takes on a stereotypical female role in his friendship with Howard as well as in the group of four men. Raj later dates Lucy (Kate Micucci), who also suffers from social anxiety, but it eventually ends; he later speaks to Penny without alcohol and thus overcomes his selective mutism. He begins dating Emily and their relationship later becomes exclusive. Raj also has a Yorkshire Terrier named Cinnamon.
The show originally centered on five characters living in Pasadena, California: Leonard Hofstadter and Sheldon Cooper, both physicists at Caltech, who share an apartment; Penny, a waitress and aspiring actress who lives across the hall; and Leonard and Sheldon's similarly geeky and socially awkward friends and co-workers, aerospace engineer Howard Wolowitz and astrophysicist Raj Koothrappali. Over time, supporting characters were promoted to starring roles, including neuroscientist Amy Farrah Fowler, microbiologist Bernadette Rostenkowski, physicist Leslie Winkle and comic book store owner Stuart Bloom.
As Sheldon and Amy start to plan their wedding, they use decision theory to limit the stress of choosing between their competing visions for the big day. After they begin to question each other’s decisions and make deliberately provocative choices, they decide to have a simple wedding at City Hall. As they wait their turn, Sheldon changes his mind and decides he wants a first dance with Amy at a real wedding.
In the episode "The Launch Acceleration", Amy tries to use her "neurobiology bag of tricks" to increase the attraction between herself and Sheldon. In the final fifth-season episode "The Countdown Reflection", Sheldon takes Amy's hand as Howard is launched into space. In the sixth season first episode "The Date Night Variable", after a dinner in which Sheldon fails to live up to this expectation, Amy gives Sheldon an ultimatum that their relationship is over unless he tells her something from his heart. Amy accepts Sheldon's romantic speech even after learning that it is a line from the first Spider-Man movie. In "The Cooper/Kripke Inversion" Sheldon states that he has been working on his discomfort about physical contact and admits that "it's a possibility" that he could one day have sex with Amy. Amy is revealed to have similar feelings in "The Love Spell Potential". Sheldon explains that he never thought about intimacy with anyone before Amy.
Simon Helberg as Howard Wolowitz: An aerospace engineer who got his Masters at MIT. Howard is Jewish and lived with his mother, Debbie (Carol Ann Susi). Unlike Sheldon, Leonard, Raj, Bernadette and Amy, Howard does not hold a doctorate. He goes into space, training as an astronaut and serving as a payload specialist. Howard initially fancies himself as a womanizer, but he later starts dating Bernadette, and they get engaged and married. Howard also has a tendency to waste money on toys and argues with Bernadette because of his oddly low income as an engineer and her high income as a pharmaceutical biochemist.