Social scientists have much to contribute to the analysis of the real and potential contribution of pre‐exposure prophylaxis (PrEP) to HIV prevention around the world. Beyond just a matter of clinical efficacy and getting pills into people's mouths, PrEP raises a number of important social‐psychological questions that must be attended to in order to translate biomedical and clinical findings into uptake of PrEP among enough people at risk of HIV infection to produce population‐level effectiveness. PrEP is a dynamic phenomenon with “dialectical” attributes that invite both optimism and cynicism as a desirable and effective HIV prevention strategy. PrEP disrupts traditional notions of “safe” and “unsafe” sex; it confers on its users a level of agency and control not generally achieved with condoms; and it affects sexual practices and sexual cultures in meaningful ways. As these dynamics play out in different contexts, and as new modes of PrEP administration emerge, it will be important for social scientists to be engaged in assessing their impact on PrEP implementation and effectiveness.