Preexposure prophylaxis is defined as the administration of antiretroviral medications to individuals who are not infected with human immunodeficiency virus (HIV) and are at the highest risk of acquiring HIV infection. In combination with other proven HIV-prevention methods, preexposure prophylaxis may be a useful tool for women at the highest risk of HIV acquisition. Obstetrician-gynecologists involved in the care of women using preexposure prophylaxis must reinforce adherence to daily medication. The Centers for Disease Control and Prevention's guidance for preexposure prophylaxis is likely to evolve in the coming years, and obstetrician-gynecologists should remain aware of new developments in this area. Risk reduction for all women at risk of HIV infection should include counseling about testing, safe-sex practices (including condom use), and other behavioral interventions.