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Cytochromes P450 (CYP) are a superfamily of haem-containing proteins distributed widely throughout nature. Historically, they have a central role in drug metabolism and following the advent of genomics they have been shown to have key roles in the biosynthesis of natural products which are used as medicines. Herein, we provide an overview of CYP systems with particular emphasis on their role as drug targets, their involvement in drug biosynthesis and potential strategies for developing new derivatives of drugs based on CYP engineering. The applied importance of CYPs for medicinal and biotechnological applications will also be discussed.