Acting for Two: In-universe use. Wil Wheaton plays two roles in the (fictional) B-MovieSerial Ape-ist 2: Monkey See, Monkey Kill. One is a Mad Scientist who attempts to resurrect Penny's character from the original film by cloning her DNA. Bringing her back as a Half-Human Hybrid. The other is an orangutan that fights the Hybrid.
In Season 1, Episode 3, "The Fuzzyboots Corollary," Leonard says that if anyone asks why Sheldon cancelled, Sheldon had a chicken carbonera sub at Quizno's for lunch. Jim Parsons gained internet infamy for his squicky appearance in the "Hungry Like the Wolf" Quiznos commercials.
In one episode, Kaley Cuoco's character Penny is talking about an upcoming play and says, "This could be my only chance to play Anne Frank." In 8 Simple Rules, Kaley Cuoco's character Bridget was Anne Frank in her school play.
Penny later got a commercial gig that showed her riding horses. Kaley is an avid rider, and in fact broke her leg the previous season after she fell and the horse trotted over it.
Courtney Ford showed up as a geeky girl and made a reference to Superman. Ford is not only quite geeky herself, but is married to Brandon Routh of Superman Returns.
In an early episode, the boys consider recruiting "TV's Blossom" (Mayim Bialik) to their Physics Bowl team, as Raj has heard she has a Ph.D. in "neuroscience or something." Dr. Bialik does, in fact, have a Ph.D. in neuroscience, and later appeared on the show as Amy Farrah Fowler, a neurobiologist. After the Bialik suggestion gets shot down, he then suggests "that girl from The Wonder Years" and Danica McKeller later had a guest spot as Abby, one of the girls Sheldon meets and are impressed by his Green Lantern's limited edition Lantern.
Sara Gilbert appears throughout the series as Leslie Winkle, a sort of friend-with-benefits for Leonard. She and Johnny Galecki (Leonard) played supporting roles on Roseanne, in which they played a couple (eventually married) with essentially the same dynamics of passive guy/sarcastic dominating girl. Amusingly, Chuck Lorre previously worked on Roseanne as a writer and producer.
Sheldon makes reference to the theme to Teenage Mutant Ninja Turtles (1987) as being his favorite tv theme song. A lesser known fact of creator Chuck Lorre is that he used to be a music composer for kids shows before he got into sitcom writing, and one of his songs actually was that theme.
Actor-Shared Background: Raj was originally going to be an American-born Indian until Nayyar was cast, with him being much more Indian (actually raised in India) than planned. Jim Parsons is also from Texas like Sheldon is and although Parsons' accent doesn't come in very often with Sheldon, Sheldon's mother and sister have very thick drawls. Mayim Bialik, who plays neurobiologist Amy Farrah Fowler, has a PhD in neuroscience.
Given that it's still currently running, has syndication deals and concurrent cable syndication, you'd think it's required by law that some channel be running this show 24 hours a day.
In Australia, the Nine Network has this feeling toward the series; it usurped Two and a Half Men as their go-to filler whenever there's a gap in the timetable, and between the main Nine channel and its spillover GO!, it's shown with incredible frequency.
It's in constant looping on the UK's "E4" channel as well. Not just one loop either, but two. The loops are deliberately out of synch so that one might be in Season 3, while the other is still in Season 1.
TNT Spain is also fond of the series, to the point it aired a marathon of each of the previous nine seasons right before the premiere of the tenth.
In the U.S. it's replaced The Office (US) as TBS's Tuesday night marathon show.
Casting Gag: Judd Hirsch as Leonard's father. Johnny Galecki mentioned in interviews that he was inspired by Hirsch's role in Taxi when it comes to being the Straight Man of the cast, and was influential in bringing him on the show.
Cast the Expert: When Amy Farrah Fowler was first introduced, the writers hadn't decided what her job was. It was finally decided that she would be a neurobiologist after the writers realized that Mayim Bialik actually held a Ph.D in neuroscience.
The Character Died with Him: Carol Ann Susi, who played Debbie Wolowitz, died in November 2014. Her character died with her. In the episode "The Comic Book Store Regeneration", it is revealed that Mrs. Wolowitz died in her sleep while visiting relatives in Florida.
Leonard has been shown playing the cello, Howard and Sheldon both play the piano. And they sing!
Amy plays the harp and sings as well.
Penny once gave Sheldon a drink that he didn't know was alcoholic, to give Jim Parsons an excuse to play the piano and sing in the Cheesecake Factory.
Simon Helberg is a brilliant impressionist and he's been given the opportunity to demonstrate it. Memorably, he does a Stephen Hawking impression in an episode where he later appeared As Himself, with Helberg having to do the impression with Hawking on set watching him off camera, and "The Love Spell Potential" features Howard as the DM for a Dungeons & Dragons game, allowing him to show off excellent impressions of Nicolas Cage, Al Pacino, and Christopher Walken, along with other hilarious voices and sound effects (much to Sheldon's delight).
Jim Parsons shows off his fantastic drumming skills on a pair of bongos in "The Werewolf Transformation".
Creator Thumbprint: In "The Gothowitz Deviation", Leonard, Sheldon, and a confused Penny are watching the fictional anime "Ochikurru: Demon Samurai". In series creator Chuck Lorre's other most famous show, Two and a Half Men, Charlie was once hired to write the theme song for the show when it was being developed.
Defictionalization: The gang plays a card game called "Mystic Warlords of Ka'a". An actual card release is planned, and the game can currently be played on Facebook.
Development Gag: In the Season 3, special features the cast does a fortune cookie Q&A about their lives and favorite moments on the show, which looks to be ad libbed. Simon (Howard) makes a joke while reading a fortune cookie "Help, I'm trapped in a fortune cookie factory!" This same joke is referenced in the fourth season as a joke that Howard is always saying and trying to get a laugh from people.
Fake Nationality: Averted with Raj (Kunal Nayyar is British-born, but really was raised in India), but played straight with other members of the Koothrappali family who've appeared to date:
British-Israeli Brian George and British actress Alice Amter play Indians.
Aarti Mann (Raj's sister Priya) was born and raised in Pittsburgh.
I Knew It!: Anyone who had watched Happy Days, saw the episode with Howard's half-brother coming. Thankfully, unlike in Happy Days, the half-brothers aren't both Howard Wolowitz with one going by a nickname to differentiate himself.
In Memoriam: The ninth episode in the eight series, The Septum Deviation, incorporates homage to Carol Ann Susi (voice of Debbie Wolowitz) who sadly died during the screening of the new season. See here.
Life Imitates Art: Johnny Galecki (Leonard) and Kaley Cuoco (Penny) actually did date for two years; they did so in secret and only revealed it after they had separated.
The 100th episode, "The Recombination Hypothesis", in which Leonard decides he wants to get back together with Penny.
The 200th episode, "The Celebration Experimentation", where Sheldon celebrates his birthday for the first time. Includes guest stars Adam West and Stephen Hawking, and the return of Leslie Winkle after six seasons.
One of Us: Nobel Laureate George Smoot made an appearance on the show after expressing his love of the show to the producers, with the episode actually written for him.
Melissa Rauch said she was a fan of the show before she was cast as Bernadette. On the other hand, Mayim Bialik admitted she didn't watch the show before she auditioned.
Real-Life Relative: In the 2013 Valentines Day episode Kaley Cuoco's sister Briana played an ex-friend of Penny's named Gretchen with whom an ex-boyfriend of cheated on her with.
The Red Stapler: When Sheldon wears a T-shirt, people want it. The same goes for items like the periodic table shower curtain or the Cylon toaster.
Romance on the Set: Johnny Galecki and Kaley Cuoco — yes, Leonard and Penny. However, they kept it secret until after they broke up... which was around the time their characters first got together. (They kept it secret because of the work environment and remain friends.)
Scully Box: As is normal for exceptionally small actresses being paired against taller actors, Bernadette is almost never seen without some sort of lift in her shoes.
Those Two Guys: Johnny Galecki and Sara Gilbert pairing up for a while in Season 2; they played love interests and eventually husband and wife on Roseanne and dated in real-life (Gilbert admitted Galecki was her Last Het Romance).
A noted aversion. The cast has said that they know almost as much about the nerd culture references as they do the technobabble — AKA, nothing. Going off-script would be suicide.
Melissa Rauch said that her vocal pitch for Bernadette was based on her mother's voice and thought it would fit the character, though she decided not to push it by including a New Jersey accent.
In "The Boyfriend Complexity" Sheldon angrily tosses a large stack of loose papers in the air in frustration over hard work that was ultimately pointless. As the pages floated to the ground one managed to perch perfectly on his shoulder, and Parsons managed to stay in character long enough for that shot to remain in the final cut (trying to stare in anger at Galecki, he wasn't able to say his next lines without cracking up).
The, somewhat infamous, spanking scene with Sheldon and Amy was not originally going to be on camera. The episode was supposed to have a Running Gag of hearing Sheldon taking care of Amy and having some Innocent Innuendo implied coming from the bathroom as the audience listens from the main room. As filming for the episode began the joke wasn't working the way they wanted it to and so they ended up actually showing the scene in front of the audience. The other cast members commented that they would emerge from their dressing rooms and were shocked.
One episode featured the guys telling Penny about General Zod when Kunal ad-libbed "Good story," despite the fact that Raj can't talk to women. He immediately covered his mouth in shock, keeping the moment (roughly) in-character.
What Could Have Been: The original (unaired) pilot for the series was quite different; Sheldon and Leonard were the only carry-overs. The Penny role was a girl named Katie (played by Amanda Walsh), a hard drinking party girl who was a new roommate and the guys would help her break out of her shell. Leonard and Sheldon's only friend was a female co-worker named Gilda (Iris Bahr) who had a crush on Leonard, felt threatened by Katie's presence, and had once slept with Sheldon (who wasn't asexual). Lastly, the set design was much darker with them living in a very run-down building. Test audiences hated Katie but really liked Leonard and Sheldon, which gave them a rare opportunity to revise the concept with a second pilot. Many of the same jokes and lines of dialogue were reused in the first season, especially the introduction to the guys' white boards and their argument over the number of dimensions used.
Kaley Cuoco was considered for the role of Katie, but was busy with other things at the time and it was felt the cynical character wasn't a good fit for her. When creating Penny they actually had Kaley in mind to reflect a much more bubbly and warm individual, to avoid the trappings of the Katie disaster.
Bill Prady said that Kevin Sussman (who portrays Stuart) was a runner-up for the role of Howard.
The show originated under two different concepts, one being Bill Prady's experience working with a group of eccentric computer programmers back in the 1980s and another under the idea of a young woman entering the real world of finding a job and making new friends. Realizing the key to both shows was on the secondary cast providing some contrast they decided on their own X Meets Y and combined them. After that they decided to move the genius nerds away from computers and make them scientists instead, pushing them outside a comfort zone.
The pilot had Sheldon & Leonard taking in a homeless woman who had just gone through a big breakup with the man she was living with, and deciding to reform her. Had the show continued in that direction, she would have gone along with it mostly because she had nothing better going on in her life, and would have been Leonard's and/or Sheldon's love interest.
Word of Saint Paul: The conflict in "The Love Car Displacement" centered around Howard feeling inadequate after meeting Bernadette's ex-boyfriend Glenn, played by former basketball player Rick Fox. Humorously, Fox commented that, in his mind, Glenn was driven crazy seeing Bernadette with Howard and caused a lot of self-doubt along the lines of, "How am I losing to this guy?" The character was physically in one early scene and had a couple of offscreen lines towards the end, so there is really nothing to support or contradict it.
Written-In Infirmity: Averted. When Kaley Cuoco (Penny) fractured her leg at the beginning of season 4, Penny was absent for a few episodes and no reference was made to her not being around. Once she returned the writers decided that her character would have a new bartending assignment at the Cheesecake Factory and be shot from the waist up behind the bar. A Vanity Plate was dedicated to new rules to ensure the safety of cast members, including any extreme activities (Kaley was injured while riding horses). This did result in Penny wearing fewer shorts and skirts, as Kaley got a fairly major scar from the whole thing. A scene in the first episode of season 5 shows Penny riding a horse, as an apparent in-joke.
Mayim Bialik injured her hand in a car accident before filming for season 6. Similarly to Kaley, no mention was made and they simply filmed around the injury by hiding it via camera angles and scenery obstructions.