There are compelling data suggesting that antiretroviral (ARV) drugs can prevent the transmission of HIV: 1) ARV therapy reduces the intrinsic risk of transmission by cutting down the viral load in infected people; 2) ARVs may be used to prevent transmission in uninfected subjects who experienced high risk exposures. Despite these encouraging preliminary results, there are several questions that need to be answered before recommending the use of ARV among uninfected subjects: 1) the efficacy of these strategies amongst women is not yet established; 2) the cost-effectiveness of pre-exposure prophylaxis (PrEP) in the long term is undefined since PrEP efficacy may depend on adherence; 3) treating uninfected individuals may be counter-effective, as it may increase risky behavior due to the belief that ARV drugs have unlimited protective power. In conclusion, the public-health use of ARV drugs represents a new paradigm in the field of HIV prevention. However, ARV treatment cannot be considered as a substitute for other measures for preventing transmission but a complement to individual protection. In particular, post-exposure prophylaxis may be used in selected cases, whereas PrEP appears to be a highly costly method with limited public-health potential and possible safety concerns.