The human genome has now been established to contain 57 cytochrome P450 genes. The proteins can be grouped into categories of types of substrates, including sterols, fatty acids, eicosanoids, and fat-soluble vitamins. Some P450s have also been demonstrated to have significant roles in the metabolism of drugs and chemicals. In addition to these, at least 13 can be considered to still be without apparent function with endogenous or xenobiotic substrates. The current list includes P450s 2A7, 2S1, 2U1, 2W1, 3A43, 4A22, 4F11, 4F22, 4V2, 4X1, 4Z1, 20A1, and 27C1. Limited information is available about the sites of mRNA expression of some of these orphans. Some strategies for characterization are discussed.