Genetic polymorphisms in drug-metabolizing enzymes are responsible for interindividual differences in the disposition of numerous drugs. The poor metabolizers (PMs) are derived from mutant alleles of cytochrome P450 (CYP), and those PMs are more susceptible to the development of adverse drug reactions, when the parent drug is pharmacologically active, or are showing a lack of therapeutic efficacy, when a prodrug is administered and its active metabolite(s) is not formed. This article reviews the basic knowledge of genetic polymorphisms of CYP-related drug-metabolizing enzymes and the clinical implications for a safer and more efficient drug therapy.