The 2014 World Health Organization (WHO) guidelines for postexposure prophylaxis (PEP) developed recommendations for PEP irrespective of exposure source in recognition of the need to simplify eligibility assessment and prescribing practices. Traditionally, separate PEP guidelines have been developed according to exposure type, with difference guidelines for occupational exposure, nonoccupational exposure, and sexual assault. Recognizing the need to improve uptake and completion rates for PEP, the WHO 2014 guideline does not differentiate between exposure sources, but rather provides recommendations across all exposures. Recommendations for simplifying prescribing approaches and supporting adherence are also provided. In translating this guidance into national PEP guidelines, countries are encouraged to consider the need to provide PEP in a way that maximizes uptake and completion rates.