In 1998, Dreyfus won the Best Supporting Performance in a Musical Olivier Award for his work in The Lady In The Dark at the National Theatre. In the same year he was nominated for the Ian Charleson Award for his performance as Cassius in Shakespeare's Julius Caesar at the Birmingham Rep.

Dreyfus also starred as Mr. Teasy-Weasy in the 2004 comedy film Churchill: The Hollywood Years.

In March 2006, he returned to the West End stage in a revival of Michael Frayn's comedy Donkeys' Years at the Comedy Theatre alongside Samantha Bond, David Haig and Mark Addy. He left in August of that year to prepare for his new lead role as the Emcee in a West End revival of Cabaret. In 2008 he appeared in a revival of Simon Gray's The Common Pursuit at the Menier Chocolate Factory.

From September 2009 to January 2010 he appeared in Breakfast At Tiffany's at the Theatre Royal, Haymarket, London.

Since 2012, Dreyfus has been appearing as Reverend Roger in the Sky Living series Mount Pleasant.

In 2013, he starred as Dr Pangloss in the London's Menier Chocolate Factory production of Candide. It has music by Leonard Bernstein and a book adapted from Voltaire by Hugh Wheeler. The lyrics are by Richard Wilbur, with additional lyrics by a team including Stephen Sondheim.

In February 2015, Dreyfus appeared on stage in Harvey, directed by Lindsay Posner. The production ran at the Birmingham Repertory Theatre until 21 February, before a UK tour and the West End.

In January 2016, he appeared as Dr Herdal in The Master Builder at the Old Vic Theatre.

In 2017 he voiced an early incarnation of The Master from Doctor Who in the Big Finish Productions release The First Doctor Adventures Volume One. He acted alongside David Bradley, with the box set released alongside David Bradley's appearance in Doctor Who as the First Doctor.