Regina King as Janine Davis
During season six of the comedy, Regina King played Janine Davis, a Human Resources rep who has to instruct Sheldon about sexual harassment after he has a complaint filed against him.
Bill Nye as Himself
Over the years, Bill Nye has appeared in multiple episodes of this show and each one is more funny than the one before it. In his first appearance, he accuses Sheldon's TV hero, Professor Proton (Newhart) of ripping off his own show, Bill Nye the Science Guy. Awkward!
Josh Peck as Jesse
Josh Peck is used to playing the dorky titular character on Drake and Josh, so he fit right in playing Sheldon's comic shop rival, Jesse, during season seven.
Carrie Fisher and James Earl Jones as Themselves
Carrie Fisher played herself in a star-studded episode of the comedy, in which Sheldon and James Earl Jones attempt to prank her at her home. Jones and Sheldon got along so well during his appearance that they visited a carnival and sang Disney karaoke before pranking the late Star Wars star.
Billy Bob Thornton as Dr. Oliver Lorvis
Billy Bob Thornton played Dr. Oliver Lorvis, a uruologist who gets the wrong impression from Penny, who is one of the pharmaceutical saleswomen that frequently visits his office. Thinking she is into him he decides to bring her flowers and somehow befriends the boys in the process.
Nathan Fillion as Himself
Playing himself, Nathan Fillion gets annoyed when Raj and Leonard approach him at a restaurant, ask him questions, and then take selfies.
Kevin Smith as Himself
Like Nimoy, Kevin Smith is heard but not seen on The Big Bang Theory. We heard the comic-book store owner's voice during season eight, when he called into a podcast taping to rave about the movie that Penny made with Wheaton. He even invites Penny to audition for Clerks 3!
Matt Bennett as Josh Wolowitz
Matt Bennett catches Howard by surprise during season eight, when he plays his half-brother, Josh. Howard gets upset meeting Josh, because it means his father moved on and started another family after abandoning him and his mother.
Elon Musk as Himself
Howard just so happens to meet Elon Musk in season nine when they both volunteer to serve dinner to the homeless. Playing himself, the Tesla tycoon told Howard—over some pumpkin pie—that he's constantly looking for good engineers.
Jane Kaczmarek as Dr. Gallo
During season nine, Jane Kaczmarek—who famously portrayed Lois on Malcolm in the Middle—appeared as Dr. Gallo, a psychiatrist who denies Penny's sales call. In an attempt to help, Leonard poses as one of Dr. Gallo's patients, but ends up spilling about his relationship with Penny.
June Squibb as Meemaw
June Squibb was cast as Sheldon's grandmother, Meemaw and she couldn't me more perfect for the role. The character was first referenced back in season two, but the Academy Award nominee didn't appear on the show until season nine. In the highly-anticipated appearance, Meemaw travels to Pasadena to meet Amy, but makes it clear that she doesn't like Amy since she broke Sheldon's heart in the past.
Adam West as Himself
Adam West, playing himself, makes an iconic cameo on TBBT. In the episode, Sheldon is reluctant to have a birthday party, but eventually caves, so his friends decide to surprise him by arranging for West to attend the big bash.
Blake Anderson
In season nine, Workaholics star Blake Anderson appeared as a minor character on the show, but he was a major pain in the butt for Sheldon. He played Trevor, who jumped in to the line for the Avengers movie screening in front of the guys because his friends saved him a spot. While most of the guys were fine with this, Sheldon was not, and therefore he does everything in his power to try to get Trevor to go to the back of the line.
Katey Sagal as Penny's Mom, Susan, and Jack McBrayer as Penny's Brother, Randall
Katey Sagal and Jack McBrayer's appearances made for a pretty star-studded season ten premiere. In the episode, Sagal brings things full circle by playing Penny's mom, Susan. Pretty cool, since she played Kaley Cuoco's mom on 8 Simple Rules. Meanwhile, McBrayer plays Penny's brother, Randall, who once was arrested for cooking meth.
Bill Gates as Himself
Bill Gates' cameo was so big for the show that even Sheldon didn't believe he was there! In season 11, the Microsoft CEO went to visit Penny at work, but Sheldon was adamant that the meeting was just a prank, since it was April Fool's Day. The joke was on Sheldon, who eventually did meet Gates and freaked out in the process!
Lauren Lapkus
Lauren Lapkus joined the series in season 11, playing Denise, the new assistant manager at Stuart's comic book store. Amy insists Denise teach her about comics so she can pretend she's actually interested in them. Denise also attends Amy and Sheldon's wedding as Stuart's date.
Mark Hamill
Mark Hamill probably had one of the most important guest roles on the series thus far. He portrayed himself during the season 11 finale and actually officiated Sheldon and Amy's wedding.
Jerry O'Connell as Georgie Cooper Jr.
Jerry O'Connell finally put a face to the name of Sheldon's older brother, Georgie Cooper Jr., who used to bully Sheldon when they were kids. At long last, Georgie's appearance comes after Sheldon's mother refuses to attend his wedding unless Georgie is invited.
Teller and Kathy Bates as Amy's Parents, Mr. and Mrs. Fowler
Talk about getting big names for these big parts! Kathy Bates played Amy's mother during the season 11 finale, which was all about Amy and Sheldon's wedding. Meanwhile, Teller played Amy's father, and shocked viewers during his cameo, because the usually silent magician actually spoke!