Simon Helberg is one half of the comedy duo Derek & Simon, along with Derek Waters. The two most recently starred together in the web series Derek & Simon: The Show on the comedy website Super Deluxe, which they created with comedian Bob Odenkirk.
Simon Helberg officially joined the cast of MADtv in 2002 as a feature performer. Simon Helberg's tenure on MADtv was limited to one season as his contract was not renewed for a second.
Simon Helberg appeared in the 2002 feature film National Lampoon's Van Wilder as one of the geeky students for whom Van Wilder was throwing a party.
He had a minor role in the 2003 movie Old School.
In 2004, he was in two episodes of Reno911!: Student Driver in Raineesha X and Hooker Buying Son in Not Without My Mustache.
He had a small role in Quintuplets, episode 6, Get a Job; as a man called Neil working behind the counter at a shoe shop where Paige and Patton were working.
He also played a small role in the film Walk Hard: The Dewey Cox Story as a Jewish record producer.
In 2004 he appeared in the film A Cinderella Story starring Hilary Duff and Chad Michael Murray; Simon Helberg played the minor role of Terry.
In George Clooney's 2005 film Good Night, and Good Luck Simon Helberg had a minor role where he had one line.
In 2005 he had a bit part on Arrested Development as Jeff, an employee of the film studio where Maeby works.
From 2006 to 2007, he had a minor supporting role as Alex Dwyer in the drama Studio 60 on the Sunset Strip.
In 2006, Simon Helberg appeared in a series of comical TV commercials for Richard Branson's UK financial services company Virgin Money.
Simon Helberg began playing Howard Wolowitz in 2007, as a geeky, "ladies man" with an eccentric fashion sense in the comedy series The Big Bang Theory.
He also appeared as the character Moist in Dr. Horrible's Sing-Along Blog, and had a small role in the pilot of the Judd Apatow-produced sitcom Undeclared.
In the 2009 Coen brothers' film A Serious Man he played junior Rabbi Scott Ginzler.
In 2010 he had a small role in Scott Pilgrim vs. The World. He said one line during the fight with the character of Mathew Patel.
He has also appeared on Mock The Week as a guest on the panel.
He had a minor role in the Season 4 finale of "The Guild" as one of the Game Masters ("GM").