The US HIV epidemic began in 1981. The number of HIV-infected individuals in the United States and throughout the world is increasing each year. Given the increasing number of HIV-infected individuals, knowledge of the basic pathogenesis of HIV disease and the principles of antiretroviral therapy is important for all healthcare professionals. This article describes epidemiologic trends in HIV and reviews HIV transmission, testing, and treatment. It also discusses the risk of HIV transmission to healthcare workers from occupational exposures and reviews the principles of postexposure prophylaxis used to reduce the likelihood of HIV transmission in appropriate circumstances.