Preexposure prophylaxis (PrEP) and treatment as prevention (TasP) involve the use of antiretroviral (ARV) drugs by human immunodeficiency virus (HIV)-negative and -positive individuals to reduce HIV acquisition and transmission, respectively. Clinical science has delivered a consistently high effect size for TasP and a range from 0%-73% reduction in incidence across placebo-controlled PrEP trials. However, the quality of evidence for PrEP compares favorably with evidence for postexposure prophylaxis (PEP). It is clear from treatment programs and PrEP trials that daily adherence presents challenges to a large proportion of the population. Although there are factors associated with inconsistent use (ie, younger age), they do not assist clinicians at the point of care. There are additional provider concerns about PrEP (covering cost of drug and delivery, undermining condom promotion, and facilitating resistant strains) that have delayed widespread acceptance. These issues need to be addressed in order to realize the full public health potential of antiretrovirals.