Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (TDF/FTC) is now accepted as an efficacious approach to preventing HIV acquisition among people at high risk of HIV infection but, in most places, PrEP uptake to date has not been sufficient to have a large effect on HIV incidence. In this paper we consider several key elements of the effort to expand PrEP uptake for at-risk populations who would benefit most, such as increasing access to PrEP, integrating PrEP programs with other services, promoting PrEP persistence and developing systems for monitoring PrEP use. We used a PrEP Continuum framework to describe barriers to equitable uptake of PrEP, and to illustrate possible solutions to barriers. Access to PrEP includes regulatory issues and geographic proximity to PrEP providers. Integrating PrEP programs with other comprehensive sexual health services, through clinic-based programs or technology-based approaches, offers opportunities to identify PrEP candidates and improve linkages to PrEP care. Once at-risk people are prescribed PrEP, lowering barriers to persistence on PrEP is critical to realising the most population benefits. To understand progress and identify underserved groups and communities, systems to monitor the uptake of PrEP are needed. Making the most of a new biomedical intervention tool requires ongoing research about implementation, scale-up through multiple channels, including community-based organisations, and high-quality monitoring of uptake. We must turn to questions of PrEP implementation and continue to seek innovative approaches to reduce barriers to PrEP uptake and persistence on PrEP.