The sitcom is centered on five characters living in Pasadena, California: roommates Leonard Hofstadter and Sheldon Cooper; Penny, a waitress and aspiring actress who lives across the hall; and Leonard and Sheldon's equally geeky and socially awkward friends and co-workers, mechanical engineer Howard Wolowitz and astrophysicist Raj Koothrappali. The geekiness and intellect of the four guys is contrasted for comic effect with Penny's social skills and common sense.
Sheldon and Amy's honeymoon runs aground in New York. Penny and Leonard discover they are uncomfortably similar to Amy's parents. Raj insults physicist Neil deGrasse Tyson and starts a Twitter war.
Sheldon and Amy drive themselves crazy trying to figure out what 'perfect gift' Leonard and Penny gave them for their wedding. Raj decides he wants to settle down and asks his father to arrange a marriage for him.
The Wolowitzes' life gets complicated when Stuart starts bringing his new girlfriend home. Penny and Leonard talk about starting a family. Raj explores an arranged marriage.
When Sheldon won't tell anyone why he's never mentioned his childhood best friend, Leonard takes matters into his own hands. Bernadette and Penny take out Raj’s fiancée for dinner to get the skinny on her.
When Amy doesn’t have time to work on super-asymmetry, Sheldon goes to great lengths to ensure she’s available to work with him even it if means accidentally sabotaging her career in the process. Raj doesn’t want Howard to join him in hosting a show at the planetarium.
When Howard dresses up as Sheldon for Halloween, Sheldon seeks retaliation at Leonard and Penny's Halloween party. Leonard is shocked that Penny doesn't remember their first kiss.
Leonard is caught between a rock and a hard place when he's responsible for distributing extra grant money. Bernadette turns the backyard playhouse into a hideaway from Howard and the kids.
Sheldon tries to bond with Amy's father, but when Howard lures Mr. Fowler away with magic tricks, Sheldon has no choice but to bond with Mrs. Fowler. Raj and Anu try to get physical for the first time.
Sheldon and Amy are devastated after learning from a Russian paper that Super Asymmetry has already been discovered and disproven. Ultra-competitive Bernadette asks Stuart’s girlfriend to teach her how to beat Howard in a popular video game.
Sheldon and Amy are still down about their theory being disproven, but a VHS tape from Sheldon’s past inspires him not to give up. Bernadette turns into a pageant mom when she tries to help Howard ace his Magic Castle audition.
Penny and Leonard organize a paintball game that results in mayhem when Sheldon is jealous of Amy. Also, Koothrappali catches Anu with her ex-boyfriend, and Stuart doesn’t want to move in with Denise.
Penny’s ex-boyfriend, Zack, and his wife want a baby, but when Zack is infertile, they ask Leonard for help. Also, Koothrappali attempts to mend things with his ex-fiancée, Anu.
Sheldon and Amy are thrilled when their super asymmetry theory is proven by two physicists, until they try to kick Amy off the Nobel nomination; Bernadette has a big success at work.
Sheldon is thrilled to help Bernadette and Wolowitz navigate bureaucratic paperwork, until he discovers they are breaking the law. Also, Leonard is disappointed when his friends exclude him from a scientific project.
Penny tries to seduce an abstaining Leonard to ruin his "donation" for her ex-boyfriend, Zack, and his wife, Marissa. Also, Wolowitz, Bernadette, Anu and Koothrappali turn Koothrappali's canceled bachelor party into a couple's trip.
The gang finds out Wil Wheaton hosts a celebrity Dungeons and Dragons game involving William Shatner, Joe Manganiello, Kareem Abdul-Jabbar and Kevin Smith. Deception and betrayal are the path to make it to the one open seat.
When Penny and Bernadette go to San Diego for a pharmaceutical sales convention, Wolowitz is in charge of the kids. Also, Sheldon finds a book on experimenting on kids, and the guys plus Amy make a day of it.
When competitors Pemberton and Campbell charm America on a publicity tour, Sheldon and Amy try to bring Nobel laureates Kip Thorne, George Smoot and Frances Arnold to their side. Also, Halley's fear of the dark leads to opportunity and conflict for Howard, Bernadette and Stuart.
The concept of what it would mean for women everywhere if Amy were to win a Nobel Prize causes Amy to have a meltdown. Also, Koothrappali and Wolowitz try to relive the good old days after Wolowitz buys a scooter that looks like the one he had years ago.
Koothrappali is worried people won’t take him seriously in his own field after publishing a paper that suggests he may have discovered alien life. Also, Leonard wants to be the principal investigator on a plasma physics study.
Kripke has proof that Dr. Pemberton plagiarized his thesis in college, and Sheldon and Amy aren't sure if they should turn him in or not; Wolowitz learns that Bernadette wasn't the only waitress at the Cheesecake Factory who had a crush on him.
Leonard is pleasantly surprised when Beverly comes to visit and she's genuinely kind to him, until he finds out the real reason she's there. Also, Denise and Stuart overstay their welcome at the Wolowitz house.
Sheldon and Amy await big news.
Johnny Galecki and Kaley Cuoco will lead fans on a trip down memory lane, sharing some of the best-kept backstage secrets and personal memories from the past 12 years.