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Preexposure prophylaxis is a powerful biomedical intervention for prevention of human immunodeficiency virus. However, its implementation has been slow and uneven in the United States. Research into innovative agents, formulations and implementation, for preexposure prophylaxis, is ongoing, and a number of new and improved methods of delivery have been developed. However, the delivery of preexposure prophylaxis primarily by nurses, has not received much attention. We overview the global evidence and programs for nurse-led preexposure prophylaxis, and propose this as a feasible and promising implementation strategy for the United States.