Transmission of HIV is critically dependent on the level of HIV viral load within blood and genital secretions. Antiretroviral therapy results in sustained reductions in viral load to undetectable levels. Thus, antiretroviral therapy has long been postulated as a potential means to curb HIV transmission. Observational data have now confirmed that antiretroviral therapy is associated with a decrease in transmission among heterosexual serodiscordant couples, injection-drug users, and in population-based studies. Mathematical models suggest that further expansion of antiretroviral coverage within current guidelines can play a major role in controlling the spread of HIV. Concerns regarding the potential for transmission during acute HIV infection, behavioral disinhibition, and resistance to overcome the impact of treatment on prevention have not materialized to date. The Joint United Nations AIDS (UNAIDS) program has called for the inclusion of antiretroviral treatment as a key pillar in the global strategy to control the spread of HIV infection.