He made the quarterfinals of Wimbledon in 1997, whilst his final junior tournament was winning Eddie Herr later that year.

His best performance in Grand Slam singles competition was at the 2002 Wimbledon championships, where he reached the semi-final, beating Galo Blanco, Vince Spadea, Yevgeny Kafelnikov and Britain's Greg Rusedski in five sets en route, as well as former champion Richard Krajicek.

A week later, in Medibank International Sydney, he reached the main draw, but lost to Mario Ančić in the first round.

In October, he won a Challenger tournament in Lyon, and this pushed him back into the world's top 100 for the first time in nearly two years.

In March, he won the doubles title in the Indian Wells Masters with Alexandr Dolgopolov of Ukraine.

Malisse came out of retirement to play doubles at the 2021 European Open having received a wildcard alongside Lloyd Harris whom he was coaching.