Despite improvements in access to antiretroviral therapy and the use of simplified dosing regimens, HIV infection is still an important global public health problem. As a consequence, significant research efforts have been focused on the development of strategies to prevent the acquisition of HIV infection. These efforts have begun to produce results. The HPTN-052 study demonstrated the effectiveness of treating infected individuals as a means to prevent onward transmission of HIV infection. In addition, Phase 2B/3 studies have shown that the use of oral and topical antiretroviral pre-exposure prophylaxis (PrEP) can significantly reduce the acquisition of HIV infection in serodiscordant couples, young women in sub-Saharan Africa, men who have sex with men, and intravenous drug users. Despite these successes, challenges remain. Adherence to daily PrEP is variable, and some large studies have failed to demonstrate the effectiveness of PrEP in reducing HIV acquisition. Novel PrEP technologies, including sustained delivery intravaginal rings and long-acting injectable products, are being developed to try and circumvent adherence problems associated with daily PrEP regimens. The purpose of this article is to briefly summarize recent progress in the development of antiretroviral PrEP.