Genetic polymorphisms of drug metabolizing enzymes often associated with clinical alteration among individuals. Current understanding of the molecular basis of the polymorphism of drug metabolizing enzymes is reviewed, particularly on cytochrome P450(CYP). Pharmacogenetic/pharmacogenomic studies are started for the estimation of pharmacokinetics of drugs, but now expanding for a tool of individual optimization of drug therapy for both drug efficacy and safety, and also for the development of new drugs. Genotyping is a powerful tool for these purposes, but not always simple because of the existence of more than 20 alleles for a single enzyme in some cases. Accumulated evidence, however, shows that occurrences of ethnic difference are rather common for allele distribution of drug metabolizing enzymes. These data indicate the necessity of the genetic analyses of Japanese population prior to the application of the genetic information for drug therapy.