In February 2009, it was announced that Dee would be one of a trio of hosts to replace the late Humphrey Lyttelton for the summer series of I'm Sorry I Haven't a Clue (the others being Stephen Fry and Rob Brydon). He subsequently became the permanent host from the 52nd series onwards. He is also a frequent guest on QI and Have I Got News for You, which he has guest-presented ten times, and he hosts segments of the BBC's biennial Comic Relief telethon. He starred in advertisements for John Smith's Bitter in the 1990s, becoming known as "the midget with the widget". He made his stage debut in 1998, playing Yvan in Yasmina Reza's Olivier award-winning 'Art'. He later returned as Serge for a 13-week run at the request of the director.
In February 2009, Dee and several other entertainers wrote an open letter to The Times supporting Baháʼí leaders, then on trial in Iran.