HIV pre-exposure prophylaxis (PrEP) is an increasingly important part of the HIV prevention armamentarium. Issues with PrEP, however, include access. We propose that one way to surmount this issue would be to have nurses provide PrEP. Although clinical guidelines exist for PrEP, they are overwhelmingly not targeted to nonprescriber clinicians. In this article, we overview current U.S. and Canadian PrEP guidelines and provide explicit guidance about how nurses can provide PrEP, including the clinical pathways and medical directives we use in our clinic. We call nurse-led provision of PrEP, PrEP-RN (Pre-Exposure Prophylaxis-Registered Nurse) and feel it may be an important step forward in HIV prevention.