Grunberg has had guest roles in television starting 1990. From 1998-2002 he appeared as Sean Blumberg on Felicity. He appeared from 2001-2006 as Eric Weiss on Alias. He left that series as a regular to star on the NBC sitcom, Grand Union. Since 2003, Abrams had planned a series called The Catch about a bounty hunter, starring Grunberg in the lead role. Suggested for both the 2004–2005 and 2005–2006 seasons, the series was never produced; however, a pilot episode was shot. Abrams also cast Grunberg in a brief role as the pilot for the 2004 series Lost. Grunberg returned for the first-season finale, but his scenes were cut for time, and were instead included on the season 1 DVD set. He also appeared in a small role in Mission: Impossible III, which Abrams directed.

Grunberg has a major role in the NBC TV show Heroes. He plays police officer Matt Parkman, who can hear other people's thoughts. Grunberg has also guest starred on House. He was offered a part in Star Trek, which Abrams will be directing, but was unable to take it because of a conflict with another project he is working on. Grunberg voices FBI agent Ethan Thomas in the video game Condemned: Criminal Origins.

Grunberg was born in Los Angeles, California, the son of Sandy (née Klein) and Gerry Grunberg,[2] and had a Jewish upbringing. He is married to Elizabeth Dawn Wershow and has three children.

While appearing on G4's Holiday Hit List in 2003, Grunberg stated he is the only man in Hollywood with four g's in his name.