Recent advances in the study of human cytochromes P450 by protein purification, molecular cloning techniques and analysis of polymorphisms has led to increased understanding of the role of the various forms in the metabolism of clinically important drugs. In particular, the substrate specificity of one form, CYP2D6, is well established. CYP2D6 shows polymorphism, with 5-10% of Caucasians (poor metabolizers) not expressing this enzyme. The molecular basis of this deficiency is now well understood and methods for the detection of poor metabolizers are discussed, as well as the effect of the polymorphism on drug metabolism. Substrate specificities and possible polymorphisms in other cytochromes P450 are also discussed.