Although the 1998 Centers for Disease Control and Prevention's guidelines for treatment of sexually transmitted diseases recommend offering postexposure prophylaxis for human immunodeficiency virus (HIV) infection following sexual assault, there are no detailed protocols on how to provide this treatment. Postexposure prophylaxis has been shown to lower the risk of seroconversion following occupational exposure to HIV by 81%, but has not yet been evaluated following sexual exposure. Though scientific data are limited, victims of sexual assault should be given the best information available to make an informed decision regarding postexposure prophylaxis. When the choice is made to take medications to prevent HIV infection, treatment should be initiated as soon as possible, but no later than 72 hours following the assault, and should be continued for 28 days. HIV postexposure prophylaxis should be provided in the context of a comprehensive treatment and counseling program that recognizes the physical and psychosocial trauma experienced by victims of sexual assault.