Physical-dependence-based theories of addiction regard compulsive drug taking as the behavioral manifestation of a desperate need to relieve aversive autonomic withdrawal symptoms. In the present article, the withdrawal-relief paradigm, or opiate model of addiction, is critically examined in the light of recent experimental and clinical evidence for various addictive drugs. It is concluded that contrary to the opiate model, the constellation of pathological behaviors defining addiction (compulsive drug use, craving, loss of control, and a persistent tendency to relapse) does not primarily reflect a need to relieve actual or conditioned autonomic withdrawal symptoms. Recent theories of addiction emphasize the positive reinforcing properties of drugs and sensitization of brain dopamine systems rather than negative reinforcement or drug-opposing neuroadaptations. Despite the failure of the opiate model, recent evidence suggests that persistent drug-induced changes in the physical brain may underlie addictive behavior, consistent with the general notion of addiction as a physical disease.