Judd Apatow's sequel to Knocked Up centres on Paul Rudd and Leslie Mann's bickering married couple Pete and Debbie, and is set a few years after the events of the first film.
"He's an ageless, classic beauty, like the grandson of Humphrey Bogart or something," O'Dowd joked to Vulture. "I guess we came to him a little bit later.
"Clueless was big, but I remember him for Friends and the early Judd stuff. He's just always so good. He's one of the few people who can play the straight man and the funniest guy in the scene equally well."
This Is 40 is out now in the US, and will be released on February 14 in the UK.
Watch the trailer below: