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Izzard's works include stand-up sets Unrepeatable, Definite Article, Glorious, Dress to Kill, Circle, Sexie and Stripped. Izzard had a starring role in the television series The Riches as Wayne Malloy and has appeared in many motion pictures such as Ocean's Twelve, Ocean's Thirteen, Mystery Men, The Cat's Meow, Across the Universe, and Valkyrie.

Izzard's main comedy role model is Monty Python, and John Cleese once referred to Izzard as the "Lost Python". In 2009, Izzard completed 43 marathons in 51 days for Sport Relief in spite of having no prior history of long-distance running.