Since the introduction of the first antiretroviral agent for HIV treatment, information on antiretroviral therapy (ART) effectiveness has grown continuously. In recent years, there has also been a growth of interest in use of ART for the prevention of HIV transmission, either by reducing the infectivity of the infected person or by protecting the uninfected individuals from HIV acquisition. The purpose of this review is to summarize the body of evidence available for treatment as prevention and pre-exposure prophylaxis and their effectiveness in prevention of infection. In addition, our aim is to discuss the operational aspects of both prevention strategies and to provide commentary for future HIV prevention programs.