Progressive changes in diagnostic and statistical manuals have formed a basis for the acceptance of substance-related disorders as independent diseases. Further, the interest in pharmacotherapies for treating addictive disorders reinforces the credibility of their disease state. A rational approach to addictive disorders requires an understanding of the etiological nature of or vulnerability to the development of compulsive drug use and brain mechanisms involved in the loss of control evident in addictive drug use. Specific areas in the limbic system of the brain appear to be responsible for drug and alcohol use, namely, the mesolimbic pathway, which extends from the ventral tegmental area to the nucleus accumbens. Environmental factors and genetic predisposition also play a role in the development of addictive disorders. Perhaps the most rational basis for medication development involves the identification of neurochemical pathways underlying the addictive use of drugs and alcohol. Medications used to treat addictive disorders can be classified according to clinical uses and brain actions. Clinical uses generally include the treatment of acute withdrawal (detoxification) and relapse prevention (addiction). The most prevalent form of addiction treatment employs abstinence-based methods. Medication trials of methadone, disulfiram, and naltrexone are discussed, along with the natural history of relapse and treatment response. Characteristics of medications used to treat addictive disorders are noted. 38 references and 1 table