Multiple forms of CYP exist in humans. P450s comprise a superfamily of enzymes. These P450s play important roles in the oxidation of structurally diverse endobiotics and xenobiotic chemicals including anticancer drugs and carcinogens. The genes encoding most of the CYP1, CYP2, and CYP3 families show genetic polymorphism. In this article, we describe recent findings that these polymorphic enzymes can abolish or quantitatively or qualitatively alter drug metabolism in humans.