Preexposure prophylaxis (PrEP) with tenofovir and emtricitabine has been shown to be effective and cost-effective in preventing acquisition of HIV infection. However, PrEP has not yet been widely adopted in the clinical practice setting. Data thus far, although imperfect, do not indicate an increase in risk behaviors in the setting of PrEP, although potential risk compensation outside of the clinical trial setting should be further examined. Substantial work remains to implement and support PrEP use, including identification of optimal settings for providing and managing PrEP, identification of methods to ensure optimal adherence to treatment, and employment of strategies to deliver PrEP to populations at greatest risk. This article summarizes a presentation made by Raphael J. Landovitz, MD, MSc, at the 2015 Conference on Retroviruses and Opportunistic Infections held from February 23 to February 26 in Seattle, Washington.