Pharmacogenetics is the study of the role of genetics in inter-individual variability to drug response and therapy. This review provides a comprehensive report of the present status of pharmacogenetic studies for opioid drugs. Opioid analgesics are widely used clinically for pain management, and inter-patient variability with opioid therapy is often reported. Information on genetic polymorphisms in enzymes, receptors and transporters related to opioid disposition (pharmacokinetics) and pharmacology (pharmacodynamics) is discussed. Pharmacogenetics of enzymes, including the cytochrome P450s and uridine diphosphoglucuronosyltransferases, opioid receptors and the ABC family of transporters, is reviewed. The role of genetic variability in clinical opioid therapy is examined, and relevant clinical trials cited. The present status of opioid pharmacogenetics, promises and challenges and future directions are discussed.