Drug users with HIV infection pose an important clinical challenge for primary care practitioners, the provider group that is particularly well situated to supply comprehensive care both for HIV-related conditions and substance-abuse problems. It is important for primary care clinicians to be familiar with the full spectrum of HIV-related disease in drug users, especially concerning bacterial infections, tuberculosis, and sexually transmitted diseases, and with the medical complications of drug use, which may mimic, mask, be obscured by, or simply coexist with HIV-specific conditions. Primary care providers must also be familiar with screening, diagnosis, and treatment of substance-use disorders, and can play a critical role in the identification of drug-use problems and the initiation of drug treatment. An understanding of the special issues of drug interactions, self-medication, and pain management is also important for the care of drug-using patients with HIV infection. Most importantly, providers' awareness of certain common behavioral patterns, problems, and shared concerns among drug users will also help to promote favorable patient outcomes and to minimize frustration and dissatisfaction among clinical staff.