Patients may present to the emergency department (ED) for various complaints and requests related to risky sexual behavior. Such concerns may include pregnancy or infectious disease transmission, including urethritis, cervicitis, HIV, hepatitis, or others. Emergency physicians should test for pregnancy and infectious diseases, treat empirically for appropriate patients, and refer patients for counseling to reduce risky sexual behavior. Following a significant potential HIV exposure, postexposure prophylaxis (PEP) should be considered. The decision to administer PEP should be based on shared decision-making with the patient and should include assessment of the risk of the exposure and HIV status of the source patient. If the HIV status of the source patient is unknown, the source should be tested following informed consent and counseling. Patients should be referred to outpatient follow-up, including primary care, infectious disease, and if indicated, social services.