Leonard's mother Beverly visits, and he is thrilled when she takes an interest in his work. However, when he learns that she is doing research on him for a new parenting book, he is furious. He prepares to tell her how she let him down over the years, but instead chooses to accept and forgive her, and forgive himself for holding onto that resentment for so long. Beverley is touched that he forgave her and they share a genuine hug. Meanwhile, Anu gets a job offer in London. Raj prepares to fly out and propose to her, ready to follow her if she accepts. Howard stops Raj at the airport, saying there is a better match out there for him, convincing Raj to return home. Stuart and Denise are bothered by her creepy roommate Mitch, while Bernadette and Howard are tired of Denise constantly staying overnight with Stuart at their house. Stuart says he is ready to move in with Denise, and they say they love each other while convincing Mitch to move out.
Kaley Cuoco as Penny: An aspiring actress from Omaha, Nebraska. Penny moves in across the hall from Sheldon and Leonard. She waits tables and occasionally tends the bar at the Cheesecake Factory. After giving up hope of becoming a successful actress, Penny becomes a pharmaceutical sales representative. Penny becomes friends with Bernadette and Amy, and they often hang out in each other's apartments. Penny and Leonard form a relationship and eventually marry.
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.
Science has also interfered with the characters' romantic lives. Leslie breaks up with Leonard when he sides with Sheldon in his support for string theory rather than loop quantum gravity. When Leonard joins Sheldon, Raj, and Howard on a three-month Arctic research trip, it separates Leonard and Penny at a time when their relationship is budding. When Bernadette takes an interest in Leonard's work, it makes both Penny and Howard envious and results in Howard confronting Leonard, and Penny asking Sheldon to teach her physics. Sheldon and Amy also briefly end their relationship after an argument over which of their fields is superior.
After the birth of Michael, Howard and Bernadette are unsure who should stay home with the kids. Howard decides to look after the kids one day to show he has what it takes to care for them. While Bernadette falls back in love with her job on a trip to the office, Howard is quickly tired and realizes he might not have what it takes to be a stay-at-home dad. Howard and Bernadette realize neither them is ready to give up their job.
The episode opens with a short montage of clips from the series' twelve seasons, then segues to Sheldon and Amy, who are up late waiting for a call from the Nobel Committee. Following a prank call from Kripke, they are told they've won the Nobel Prize in Physics for their super-asymmetry work. The attention from the media and the university bothers Sheldon. Amy is saddened by an unflattering picture of her in a news report, so Raj convinces her to get a makeover. She loves her new look but Sheldon demands she change it back. Leonard calls him out for being rude, but Sheldon flees when he sees Penny emerge from the newly repaired elevator. Sheldon and Penny go to the Cheesecake Factory and Penny tells Sheldon that change is the only constant thing in life. On a TV, they see Bernadette and Howard take credit as Sheldon and Amy's best friends. Raj and Leonard defend Amy, with Leonard accidentally breaking Sheldon's DNA molecule model in Apartment 4A. Penny convinces Sheldon to ride in the elevator.
Sheldon's mother Mary refuses to attend his wedding unless he invites his older brother George, with whom he is no longer speaking. Sheldon and Leonard fly to Texas to talk to George, who now owns a chain of tire stores. He refuses to attend and later explains to Leonard and Sheldon that the family sacrificed a lot to fund Sheldon's education, and he was stuck caring for their mother and sister Missy after their father died while Sheldon was in college. Sheldon never thanked him for this. Leonard takes George back to the hotel room where Sheldon apologizes for what he did and the brothers reconcile. George agrees to attend the wedding. Meanwhile, Howard and Bernadette's children contract pinkeye, infecting everyone except Penny, much to Amy's fury.
Through the use of his vanity cards at the end of episodes, Lorre alleged that the program had been plagiarized by a show produced and aired in Belarus. Officially titled Теоретики (The Theorists), the show features "clones" of the main characters, a similar opening sequence, and what appears to be a very close Russian translation of the scripts. Lorre expressed annoyance and described his inquiry with the Warner Bros. legal department about options. The television production company and station's close relationship with the Belarus government was cited as the reason that any attempt to claim copyright infringement would be in vain because the company copying the episodes is operated by the government.