The majority of HIV-1 infections are acquired sexually, and interventions to prevent sexual transmission are urgently needed to curb the growth of the HIV pandemic. The potential role of antiretroviral therapy in preventing sexual transmission of HIV is still emerging. Highly active antiretroviral therapy has been shown to decrease HIV RNA shedding in the genital tract, and its use among serodiscordant couples has been associated with reduced seroconversions in partners who are HIV negative. However, other studies have associated the use of antiretroviral therapy with increased HIV transmission risk behaviors. In this review, we explore the rationale for using highly active antiretroviral therapy to prevent sexual transmission of HIV including its role in prevention strategies at the population level, as well as the cost-effectiveness and potential limitations of this approach.