PrEP (Pre-Exposure Prophylaxis) is an innovative HIV prevention strategy, which, although widely used in several countries, only constituted a pilot project in Greece. PrEP is defined as the administration of antiretroviral agents recommended for HIV-negative individuals who have a high risk of HIV infection. The aim of the present review is to highlight PrEP as a prevention treatment strategy that acts complementary to other risk reduction strategies. Specifically, clinical trial data from studies conducted during the last decade is presented and analyzed. PrEP, in all subpopulation studied and with all regimens used, significantly lowers the risk of HIV infection compared to placebo used in each study, in the 90% of the cases. No serious side effects were reported, while it was established that with adherence to the prescribed dose, the chances of prevention are greater.