Pre-exposure prophylaxis (PrEP) with antiretrovirals could prevent millions of infections, yet effective strategies to get PrEP delivered are just being defined. This editorial introduces a series of 17 articles which form a special issue of Sexual Health focused on the opportunities and challenges for health service providers engaged in PrEP prescribing. All pieces presented here share useful lessons from PrEP pioneers; more than that, they should serve as catalysts to accelerate PrEP implementation around the world.