The introduction of highly active antiretroviral therapy 10 years ago has revolutionized the treatment of HIV infection in industrialized countries. HIV infection has now become a chronic condition, often treatable with low number of pills. Pregnancy and childbirth are possible with minimal vertical transmission risk. Organ transplantation is no longer contra-indicated solely on the basis of HIV infection. New management issues have emerged, including the long-term cardiovascular risk and metabolic toxicity associated with anti-HIV medications, the appearance of drug-resistant HIV strains, and the re-emergence of risky sexual behavior, particularly among men who have sex with men. This article provides an update for primary care physicians regarding important questions and controversies in the treatment of HIV-infected patients in 2006.