This review discusses the achievements of directed evolution of enzymes relevant to natural and unnatural product chemistry focusing on the period 1998-2004, citing 156 references. A few selected papers published before 1998 are also cited for their fundamental relevance, together with additional reviews covering other aspects of directed evolution applied to closely related topics. An overview of the latest methods applied in directed evolution is given in the introduction, together with a range of approaches for the selection of variants of enzymes with desired catalytic properties. All classes of enzymes are systematically covered.