Bill Murray was Letterman's first guest on "Late Night," and the actor always makes a splash when he returns, including fabulous entrances as Liberace and Peter Pan.
Dave wasn't always safe behind his desk, as Crispin Glover proved when he showed off his kicking ability for the late-night host.
Madonna stopped by for a profanity-filled visit to the "Late Show" in 1994, where she openly discussed her sex life.
Howard Stern has stopped by numerous times to converse with his fellow talk-show host. Their lively conversations always make for entertaining TV.
Oprah stopped by "Late Night" in 2005 to put an end to her and Letterman's alleged "feud."
Drew Barrymore showed off her moves on Dave's desk -- and, for an encore, flashed the host.
What would later be revealed as an elaborate method acting job, Joaquin Phoenix's bizarre appearance in 2009 confused not only Letterman, but most of America as well.
After years of jokes when she was the first lady, Letterman welcomed Hillary Clinton to the "Late Show" when she was making her Senate run
Barack Obama became the first-ever sitting U.S. president to appear on the "Late Show" in 2009.
After a week of shooting in L.A., Letterman was reunited with his mentor Johnny Carson, who got behind the desk one last time. It would end up being Carson's last TV appearance.