Use of highly active antiretroviral therapy has resulted in significant reductions in HIV-related morbidity and mortality. Current therapeutic approaches target cellular entry, viral transcription, and maturation of newly formed virus. Combination therapy is necessary to provide durable suppression of viral replication and immune reconstitution. A variety of consensus treatment guidelines addressing prophylaxis and treatment of HIV infection and opportunistic infections have been developed to serve as resources for clinicians. A summary of U.S. Department of Health and Human Services Guidelines for Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents and International AIDS Society- USA Panel recommendations for Treatment of Adult HIV infection are presented. Considerations for selection of antiretroviral therapy in special populations (e.g., pregnancy, coinfection with tuberculosis, hepatitis B and C virus) are highlighted. U.S. Public Health Service guidelines for management of occupational exposure to HIV and initiation of postexposure prophylaxis are discussed as well as World Health Organization recommendations for use of antiretroviral therapy in resource-limited settings. The pathophysiology of HIV infection, viral load testing methods, viral dynamics, and classification of antiretrovirals are also briefly reviewed.