In the past 15 years there has been an explosion of data on the multivariate nature of drug dependence. The complex relationship between addictive disorders and psychopathology has been better clarified. Certain Axis I and II diagnoses in DSM-III appear to occur more commonly in alcohol-and drug-dependent patients than in the general population, suggesting that they may serve as risk factors for the development of addictive disorders. Psychopathological symptoms also result during periods of chronic intoxication and may persist as secondary psychiatric disorders even in the absence of continued substance use. Behavioral research in human and animal models has begun to yield insights into the nature of dependence disorders and the importance of brain mechanisms of reinforcement to the addiction process. Inevitably, neural scientists are beginning to delineate the commonalities and differences in drug reinforcement across drug class. The research has begun to suggest pharmacological approaches to the treatment of drug dependence and withdrawal. This paper provides an overview of research on the psychobiology of drug dependence with implications for the clinician.