While in his final year of drama school, he made his film debut in Shadowlands (1993) after being spotted by Richard Attenborough. He was nominated for Best Actor at the 1995 Venice Film Festival for his performance as a Northern Irish terrorist in Thaddeus O'Sullivan's film, Nothing Personal (1995), and for Best Supporting Actor at the Genies in Toronto for his performance in István Szabó's Sunshine (1999).
He has appeared in a number of television series, such as Armadillo (2001); 24 (2005); Invasion (2006); and The Closer (2006). His more recent roles include Thomas Cromwell in Showtime's The Tudors; the villainous Billionaire 'Chess' in the NBC superhero/crime drama series The Cape; heroic Templar Sir Gregory in the Syfy original film Dark Relic (2010); and vampire Franklin Mott in the HBO drama True Blood. In season 2 of Grimm, Frain joined the cast as a mysterious recurring character named Eric Renard.
He has been a regular on the stage in the United Kingdom, appearing with the Royal Shakespeare Company and Royal Court Theatre, as well as on the West End. He has also appeared on Broadway and was a recipient of the 2008 Drama Desk Award for Outstanding Ensemble Performances along with the rest of the cast of The Homecoming (2007).
