Injection drug use is an efficient and ongoing means of HIV transmission and is the principal mode of transmission in some parts of the world. In the United States, approximately 10,000 injection drug users are believed to acquire HIV each year. The US Public Health Service hopes to decrease all HIV transmission in the United States by 50% in the next 5 years, by promoting care and prevention services to infected persons. Subtle differences in the virology and immunopathogenesis of HIV between injection drug users and other groups at risk are still being investigated. So far such differences have no practical implication. Comparison of progression rates and survival with HIV across risk groups has been difficult because of the many competing causes of death unrelated to HIV among injection drug users, but overall HIV disease progression rates are similar across risk groups, after adjusting for age. Some AIDS-related opportunistic infections are more common (such as tuberculosis) or less common (such as Kaposi's sarcoma) among injection drug users, based on rates of exposure and latent infection. Other comorbidities, including chronic psychiatric disorders and hepatitis C disease, are more common among injection drug users than among others with HIV infection. Highly active antiretroviral treatment seems to be as effective in persons with a history of injected drug use as in others. Increasing the numbers of HIV-infected injection drug users who know their diagnosis, increasing their access to care and prevention services, and increasing their adherence to a therapeutic regimen are the current challenges in confronting the HIV-epidemic among injection drug users. To overcome these obstacles, clinicians must have both technical knowledge and skill in assisting patients with behavior change.