We met Sara Gilbert's Leslie Winkle in the very first season of our scientific-themed comedy, and she definitely brought the laughs with her quick insults and dry wit. After an on-again, off-again relationship with Leonard and a brief flirtation with Howard, Leslie's snarky personality has not been seen since the third season.
No one truly understands Sheldon's wacky ways quite like his mother, Mary Cooper. First appearing in the fourth episode of the first season, Laurie Metcalf has been in numerous episodes as a Texas-loving, born-again Christian who knows exactly what to say to reign in Sheldon's over-the-top personality and at-times stubborn behavior.
As Leonard's manipulative girlfriend from season two, Sara Rue played Stephanie Barnett. She was a doctor who used sex as a weapon to move their relationship forward very quickly. Although Sheldon liked Stephanie, he did not realize that she was using her status as a doctor to dish out fake advice as a way to alter his annoying habits,
Beverly Hoffstadter, M.D., Ph.D.—portrayed by Christine Baranski—is Leonard's strict and overly logical mother. She first appeared in season two and we learned that her job as a psychiatrist combined with her analytical nature drives everyone crazy except for Sheldon.
Charlie Sheen appeared as himself on the fourth episode of the show's second season. In the episode, Raj runs into Sheen at a bar and tells the actor that he's going to be in People magazine.
Octavia Spencer has an annoying encounter with Sheldon in season two when playing an irritated DMV clerk who has to deal with the scientist, who is trying to get his learner's permit.
A somewhat bitter entomologist at the university, Professor Crawley's (Lewis Black) fascination with bugs as a child earned him the nickname "Creepy Crawley." In season three, Howard and Sheldon ask the professor to identify the species of a cricket they caught in order to settle a bet.
Wil Wheaton, best known as Wesley Crusher on Star Trek: The Next Generation, has appeared in several episodes of Big Bang since his debut as Sheldon's nemesis in season three. Throughout the years, Wil's relationship with Sheldon has changed from bitter rivals to good friends.
Known to geeks all around the world as Battlestar Galatica's tough and sexy Kara Thrace, Katee Sackhoff has appeared in two episodes of BBT as one of Howard's sexual fantasies. Although Katee is a manifestation of Howard's imaginations, he never has full control over her or his day dreams and both of his attempts of alone time with her have been disrupted by Mrs. Wolowitz's yelling.
Abby, played by Danica McKellar, was a Caltech science grad student/employee and a big fling of Raj's in season three. When Raj bribed Sheldon to accompany him to an employee mixer, they met Abby and her friend Martha, hit it off and shared an epic Rock Band performance. Although Raj and Abby shared a sweet make-out sesh, we haven't heard from her since.
Appearing as a disgruntled version of himself, Stan Lee guest starred in season three when Penny and Sheldon surprise him at his home in an attempt to get his autograph. Sheldon does end up getting Stan's autograph, and he seems even more delighted by the fact that the signature is on a restraining order.
Appearing in the third season, Dr. Plimpton (Judy Greer) was a cosmological physicist from Princeton University, who came to Pasadena as a friend and personal guest of Sheldon's. At first she seems socially dysfunctional, but her personality took a turn for the crazy when she tried to seduce Howard, Leonard and Raj in a four-way sexcapade.
There might be one thing The Walking Dead's Steven Yeun hates more than zombies...Sheldon Cooper. In a season three, Yeun played Sheldon's former roommate, Sebastian, who tried to warn Leonard about moving in to their apartment.
Known by Star Trek fans as Mr. Sulu, George Takei popped up in the fourth season in one of Howard's infamous sexual fantasies. George and Katee Sackhoff represented Howard's subconscious that wanted him to get back together with Bernadette.
It's only fitting that famed astrophysicist Neil deGrasse Tyson appeared on multiple episodes of the popular program. Playing himself, Tyson makes friends with Raj, but is snubbed by Sheldon, who is upset that Pluto is no longer considered a planet.
Eliza Dushku is used to playing badass roles, so it's no surprise she appeared as an FBI agent in season four. As Agent Angela Page, she interviewed the group when Howard is trying to get government security clearance. Talk about intense!
Jessica Walter is no stranger to comedic roles, having starred on both Archer and Arrested Development. In season four of The Big Bang Theory, Walter plays Mrs. Latham, one of the top donors to the university where the guys work. When she shows an interest in Leonard, he decides he has to hook up with her so the university can get more funding.
Another amazingly appropriate recurring guest star is Reading Rainbow's LeVar Burton. The actor appears as a guest on Sheldon's webseries Fun with Flags to talk about flags from Star Trek.
Known to the Star Trek world as the half-Vulcan Mr. Spock, Leonard Nimoy was referenced on BBT countless times before finally making a guest appearance in season five. Although Leonard did not actually spear on the show, he was the voice of a collectible Spock action figure that doubled as Sheldon's conscience.
Stephen Hawking always has been, and always will be, one of Sheldon's most influential heroes, so you can imagine his extreme excitement when he finally got the chance to meet Hawking in season five. Unfortunately the brilliant theoretical physicist caught a minor arithmetic error in Sheldon's paper and Sheldon fainted in front of him out of shock and embarrassment.
In one of the funniest, yet shortest, guest spots in BBT history, Buzz Aldrin appeared as a accomplishment-boasting version of himself on a viral YouTube clip. In the video, Aldrin is seen passing out Halloween candy to a group of children and with every treat he passes out, he finds a way to connect it with his infamous trip to the moon.
Bob Newhart played Leonard and Sheldon's favorite children's show host, Professor Proton, who was known for demonstrating scientific principles using everyday objects. It was revealed that because of professor Proton's enthusiasm (and his puppet side-kick Gino the Neutrino!), both Sheldon and Leonard developed a passion for science at a very young age.
Brent Spiner may have starred on Star Trek: The Next Generation, but even that doesn't protect him from making an enemy out of Sheldon. While attending Will Wheaton's party in season five, the actor opened a signed, mint-condition action figure, immediately landing himself a spot on Sheldon's nemesis list.
Howie Mandel, playing himself, makes things a tiny bit awkward for Howard on his episode of TBBT. After returning from space, Howard hears people cheering "Howie" at the airport and assumes the affection is directed his way. Instead, he learns that journalists are just calling out for Mandel.