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.
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.
Sheldon and Amy go on their honeymoon to New York City, starting with Legoland New York. Sheldon's insistence on scheduling their marital relations stresses Amy. He says he only does it to remind himself to be intimate with her. They compromise by letting him make a schedule without sharing it with her. Leonard and Penny discover Mr. Larry Fowler (Teller) in Sheldon and Amy's apartment hiding from his wife (Kathy Bates). Leonard notices parallels in his own marriage, which offends Penny. Leonard apologizes, and Penny convinces Mrs. Fowler to give her husband a break. When Mrs. Fowler wants to hang out with her regularly, Penny scares Larry out of the building. Raj instigates a Twitter feud with Neil deGrasse Tyson but is scared off when confronted over the phone. Neil then calls Bill Nye to scare him, too.
When Bernadette tells Howard that she is expecting again, he is once again floored with fear about raising another child, particularly when he learns it’s a boy. Howard, who isn't athletically inclined, worries he will not be able to relate to a son who might one day expect his dad to be the stereotypical father. Despite his best attempts to get out of it, Howard has a vasectomy to avoid any future surprises and is placed on bed rest, joining his pregnant wife at home.
In scenes set at Howard's home, he interacts with his rarely-seen mother (voiced by Carol Ann Susi until her death) by shouting from room to room in the house. She similarly interacts with other characters in this manner. She reflects the Jewish mother stereotype in some ways, such as being overly controlling of Howard's adult life and sometimes trying to make him feel guilty about causing her trouble. She is dependent on Howard, as she requires him to help her with her wig and makeup in the morning. Howard, in turn, is attached to his mother to the point where she still cuts his meat for him, takes him to the dentist, does his laundry and "grounds" him when he returns home after briefly moving out. Until Howard's marriage to Bernadette in the fifth-season finale, Howard's former living situation led Leonard's psychiatrist mother to speculate that he may suffer from some type of pathology, and Sheldon to refer to their relationship as Oedipal. In season 8, Howard's mother dies in her sleep while in Florida, which devastates Howard and Stuart, who briefly lived with Mrs. Wolowitz.
The show's pilot episode premiered on September 24, 2007. This was the second pilot produced for the show. A different pilot was produced for the 2006–07 television season but never aired. The structure of the original unaired pilot was substantially different from the series' current form. The only main characters retained in both pilots were Leonard (Johnny Galecki) and Sheldon (Jim Parsons), who are named after Sheldon Leonard, a longtime figure in episodic television as producer, director and actor. A minor character, Althea (Vernee Watson), appeared in the first scene of both pilots that was retained generally as-is. The first pilot included two female lead characters - Katie, "a street-hardened, tough-as-nails woman with a vulnerable interior" (played by Canadian actress Amanda Walsh) and Gilda, a scientist colleague and friend of the male characters (played by Iris Bahr). Sheldon and Leonard meet Katie after she breaks up with a boyfriend and they invite her to share their apartment. Gilda is threatened by Katie's presence. Test audiences reacted negatively to Katie, but they liked Sheldon and Leonard. The original pilot used Thomas Dolby's hit "She Blinded Me with Science" as its theme song.
Turning to total viewers, “Manifest” was the biggest gainer overall, on average adding 6.1 million viewers per episode. ABC’s “The Good Doctor” was second with an average viewer lift of just under 6 million. “New Amsterdam” (5.2 million viewer lift) and “A Million Little Things” (3.5 million viewer lift) were also among the top gainers in this measure, as was ABC’s “Whiskey Cavalier” (3.2 million viewer lift).
Wil Wheaton brings William Shatner on his Professor Proton show to meet Sheldon, who gets so excited that he vomits on Shatner. Going to Wil to apologize, he finds Wil hosts a Dungeons & Dragons group with his celebrity friends including Shatner. Finding out Stuart is in the group and never told them, the guys make Stuart panic and quit. Wil secretly invites Leonard who discovers that the group also includes Shatner, Kevin Smith, Joe Manganiello and Kareem Abdul-Jabbar. Leonard tells Penny, who tells Amy and Bernadette, all three women having a crush on Manganiello. Because of that indiscretion, Wil kicks out Leonard and admonishes the guys for using him for his connections, and says that one of the worst things about being a celebrity is not knowing whether someone will like him for himself. To apologize, the guys invite Wil to play D&D with them at Leonard’s apartment, but Wil, secretly in the middle of a game with Penny, Amy and Bernadette and the group, politely turns them down, before allowing the girls to send them a photo of the events as payback.
Leonard gives an interview on public radio where he admits physics research might be at a dead end. The university is furious and, while trying to think of reasons to put in a retraction, he depresses Sheldon into thinking he might be right. Howard and Raj come over and end up just as depressed. Getting drunk with Penny, the men go to the grave of Richard Feynman and realize there is hope for physics as long as they believe in it. Leonard accidentally sends a drunken email to Human Resources. Meanwhile, Amy and Bernadette agree with each other to keep quiet about the success in their careers so as not to upset Sheldon and Howard. While bragging to each other, they end up arguing which of their fields is better.
Sheldon and Amy's wedding day arrives, with many friends and family attending, including Amy's domineering mother (Kathy Bates) and quiet father (Teller); Sheldon's mother Mary, brother George, and sister Missy, who is pregnant with her second child and separated from her husband; and Mark Hamill, who replaces Wil Wheaton as officiant as a favor to Howard who returned his lost dog. Sheldon cannot get his bow-tie to be symmetrical and conversations with Amy and his mother give him an epiphany about superasymmetry. Sheldon and Amy, along with Leonard, get caught up figuring out the math of the theory during the wedding ceremony, making Hamill take Star Wars questions to stall for time. Penny retrieves the couple, who then decide that they have the rest of their lives to make science together. Amy and Sheldon then express their vows. Amy recites a set of heartfelt vows, leaving Sheldon initially at a loss for words, before he reciprocates her loving words. They are pronounced as husband and wife.
With Leonard, Howard, Raj, and Amy accomplishing so much on their respective projects, Sheldon is forced to admit he has nothing important upon which to work. He makes Amy leave the apartment for a few days so he can focus, but cannot come up with any ideas and calls his mother as a distraction. Leonard and Amy have fun recreating experiments from when they were growing up, boring Penny, so she eats with Sheldon as he mulls over his scientific studies. Penny helps him realize that his study of dark matter is his rebound science from string theory, which Sheldon admits he never truly disregarded, but explaining string theory to her inspires Sheldon, helping him discover a potential breakthrough in the field. Meanwhile Howard is too busy with his family to be in the band with Raj, so Raj brings in Bert. But, when Howard annoys Bernadette by writing an astronaut-themed musical while she is on bed-rest, she makes him rejoin the band. The three are poorly received at a Bar mitzvah after singing Bert's original song about the boulder from Indiana Jones .
After Sheldon has a food truck moved away from the building, Leonard and Penny are shocked to find he is the leader and sole member of the Tenants' Association for the building. Amy doesn't want to be caught in the middle but secretly suggests they rally support from the other tenants to vote Sheldon out. Nobody else supports Leonard so Amy tells them Sheldon was never added to the lease when he moved across the hall with her. Sheldon fires back with his own legal technicality so Amy is forced to support Leonard. She makes Sheldon happy by saying he can be Leonard's official opposition, making Leonard believe he made a mistake. Meanwhile, Howard and Raj find a drone. Raj returns it to the cute owner Cynthia and gets her number. Unfortunately, Cynthia watches footage of Raj on the drone and is immediately turned off.