We begin with the recently deceased cultural icon, Leonard Nimoy. In Season 5, the Star Trek star acted as the voice of Sheldon's rather opinionated Mr. Spock action figure.
In Season 2, Leonard, Howard, and Raj spot Summer Glau (Firefly, Serenity, The Terminator) on a train, and promptly all make fools of themselves.
Charlie Sheen makes an appearance in Season 2, when he and Raj have a brief encounter at The Cheesecake Factory.
In Season 3, Sheldon manages to get a restraining order against him by Stan Lee.
Best known for his role on Star Trek: The Next Generation, Wil Wheaton has made more than a few appearances, most of which involve him antagonizing Sheldon. He made his first appearance in Season 3.
Neil Degrasse Tyson
Neil Degrasse Tyson, astrophysicist and host of the show, Cosmos, appeared in Season 4.
Best known for her role on Battlestar Galactica, Katee Sackoff appears in Howard's fantasies in Season 3.
Star Trek's George Takei appears in Season 3. In a fantasy that begins with aforementioned actress, Katee Sackoff, George Takei makes an accidental appearance (along with Bernadette).
Star Trek: The Next Generation's LeVar Burton is also known for hosting "Reading Rainbow." He has made a few appearances, the first of which was in Season 4. He's even taken part in "Fun with Flags."
Scientist Stephen Hawking has appeared a few times, but Sheldon first had the chance to meet his idol in Season 5.
Best known for his role on Star Trek: The Next Generation, Brent Spiner appears in Season 5 long enough to ruin Sheldon's action figure.
Astronaut Buzz Aldrin appears in Season 6, giving out Halloween Candy and bragging about walking on the moon.
In Season 6, Howie Mandell steals Howard's spotlight when he returns from space.
Bill Nye appeared in Season 7 as a rival to "Professor Proton," who was played by another special guest, Bob Newhart.
James Earl Jones
In Season 7, Sheldon gets to hang out with James Earl Jones. Included in their activities are ice cream, a ferris wheel ride, karaoke, and even playing a prank. Which brings me to...
Also appearing in Season 7, Carrie Fisher is the victim (and that's a strong word) of a prank by Sheldon and James Earl Jones.
In Season 8, Raj and Leonard try to decide if they man they run into a deli is actually Firefly's Nathan Fillion. Of course, you might also recognize Fillion from a hit show called Castle.