Pharmacogenetics is the study of inherited variation in drug response. Genetic differences in drug metabolism are the most common causes for inherited variations in drug response or adverse reactions to medications. Methyl conjugation is an important pathway in the biotransformation of many drugs. Experiments performed during the past decade showed that individual variations in the activities of enzymes that catalyze S-methylation, O-methylation and N-methylation are under genetic control in human tissue. These inherited variations are responsible for individual differences in metabolism, effect, and toxicity of drugs that undergo methyl conjugation. The approach used to study the pharmacogenetics of methylation may also be applicable to the study of inherited variations in other pathways of drug metabolism.