Individuals with a substance use disorder who are infected with human immunodeficiency virus (HIV) provide physicians with challenging issues for both medical management and drug treatment. Using a case presentation format, we present an overview of some of the major issues involved in delivering effective primary care for these individuals. A detailed medical and substance use history is critical to sort common complaints that can be seen both in HIV infection and with drug use. Physicians must be able to recognize withdrawal syndromes and differentiate those signs and symptoms that may be attributed to specific drugs. A two-phase model of drug abuse treatment takes into account both detoxification and maintenance of abstinence. Primary care physicians should be able to initiate the process of substance abuse treatment and refer the patient to appropriate substance abuse programs when necessary. Pharmacological approaches to long-term abstinence with heroin addiction include methadone, LAAM, and naltrexone. While clinically challenging, HIV-infected substance users can be successfully managed using the general principles of primary care.