Individuals with mental disorders who seek treatment in the community may receive it within the mental health service system, while drug-addicted individuals may receive treatment within the drug abuse treatment system. Those requiring treatment for both mental disorders and drug use disorders may not be able to receive comprehensive treatment in one treatment program. In addition, having separate service delivery systems and separate Federal institutes funding research on mental and addictive disorders has generally fostered the separation of mental health research and drug use disorder research. Nonetheless, research on the treatment of individuals with comorbid mental and addictive disorders holds promise for a greater understanding of the relationship between these disorders and the potential for better treatment. Specific attention is paid the influence of comorbid major depression and drug use disorders on alcohol and drug treatment and drug use patterns in persons with comorbid mental and addictive disorders. Anxiety disorders, comorbid drug abuse, and benzodiazepine discontinuation are discussed in relation to implications for treatment. Consideration is also given to cigarette smoking and its comorbidity, the treatment of depression in drug-dependent patients, the course and treatment of drug use disorders in persons with severe mental illnesses, and drug use and HIV risk among persons with severe mental illnesses. Finally, the discussion focuses on depression, drug use, and sexual orientation as cofactors in HIV-infected men and on psychiatric symptoms, risky behavior, and HIV infection. References, tables, and figures