Though a large number of antiretrovirals have been developed for the treatment of HIV infection, new HIV infections continue to occur, especially among certain high-risk groups, such as men who have sex with men. Overall, the current estimated incidence of HIV infection is 2.5-fold higher than the number of individuals that begin antiretroviral therapy every year worldwide. Along with the personal drama caused by the diagnosis of HIV infection, other considerations in society, including economics and interpersonal relationships, make the need for HIV prevention strategies a priority. Though vaccines have shown great efficacy in the combat of other epidemics, currently there is no effective vaccine against HIV, and it is unlikely that any will become available in the near future. Thus, new approaches such as pre-exposure prophylaxis are viewed with increasing interest. The results from recent clinical trials have provided support in favor of distinct pre-exposure prophylaxis modalities. However, concerns exist about increasing risky behaviors and selection and spread of antiretroviral drug resistance with a broader use of pre-exposure prophylaxis. The aim of this review is to examine the evidence available on the effectiveness of pre-exposure prophylaxis and its potential influence on the HIV epidemics.