The cytochrome P450 (P450) enzymes are critically involved in the biosynthesis of sterols, eicosanoids, and other physiologically important substances. Conversely, they are also essential for the metabolism of endogenous lipophilic substrates, such as fatty acids, as well as most drugs and xenobiotics. Cytochrome P450 catalysis is uniquely suited to the introduction of hydroxyl groups and other polar functionalities into compounds as difficult to oxidize as saturated hydrocarbons. The introduction of such functionality is particularly critical for the metabolism and elimination of lipophilic compounds lacking functional groups suitable for conjugation reactions. On the dark side, the oxidative power of cytochrome P450 enzymes not infrequently transforms innocuous substrates into chemically reactive, toxic metabolites.