Pharmacogenetic studies with drugs of abuse are proliferating. Many genetic animal models are now available for studies of the mechanisms of action of a variety of drugs. These models provide unique, genetically defined populations of extremely sensitive and insensitive animals for neuropharmacological analyses. John Crabbe and John Belknap describe how molecular biological methods are being applied to these models in combination with more traditional genetic mapping strategies to identify single genes of importance to drug effects. Pharmacogenetic approaches offer the hope of establishing commonalities of mechanisms among abused drugs.