PrEP, or pre-exposure prophylaxis, is a simple, safe, and effective option for at-risk individuals to prevent the acquisition of HIV infection. In spite of the existence of this medication, there are many barriers to accessibility and utilization; many at-risk patients not only are not taking this medication, but also have not had a discussion regarding PrEP with their clinician. In this chapter, we discuss a framework for assessing risk through a comprehensive sexual history, practical tips for prescribing the medication, and barriers to its widespread use.