HIV preexposure prophylaxis (PrEP) is an opportunity for clinicians to curb the 40,000 HIV infections occurring annually in the United States. PrEP is medication used by HIV-negative patients to reduce their risk of acquiring the virus. This article provides a baseline understanding of PrEP indications, prescribing, and monitoring, including a review of previously approved medication and an update on newly approved drugs, including emtricitabine/tenofovir alafenamide (F/TAF). Sexual and gender minorities are often underrepresented in the literature about PrEP, but clinicians should address risk focused on specific behaviors rather than population-level characteristics. As one of few professions with prescriptive authority, PAs have an obligation to understand and manage PrEP.