Alcohol withdrawal is being accomplished with safer substitution agents that are tailored to the specific medical needs of patients. Alcohol relapse prevention can be assisted with naltrexone or disulfiram. Acamprosate is not yet available in the United States, but appears to be a promising new treatment. Detoxification may be achieved with clonidine or lofexidine, either alone or with adjunctive medications, but the relapse rate is high. Long-term opioid replacement therapies are effective and include methadone, levo-alpha-acetylmethadol (LAAM), buprenorphine, and naltrexone. There is currently no effective pharmacotherapy for cocaine dependence, although the search continues. Nicotine dependence can be successfully treated with replacement agents and/or bupropion. Comorbid psychiatric illness is prevalent among addicted patients, and therapies should be tailored to treat the comorbid diagnoses, incorporating drug mechanisms and side-effect profiles to best treat the dually diagnosed individual. Care should also be taken, however, to guard against treatment of only one illness in such patients, as this will increase the likelihood of a poor clinical outcome. Pharmacokinetics, drug mechanisms of action, and addiction potential should be incorporated into a patient's pharmacotherapeutic plan. 144 references