Prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) remains a challenge in most resource-limited settings, particularly in Africa. Single-dose and short-course antiretroviral (ARV) regimens are only partially effective and have failed to achieve wide coverage despite their apparent simplicity. More potent ARV combinations are restricted to pregnant women who need treatment for themselves and are also infrequently used. Furthermore, postnatal transmission via breast-feeding is a serious additional threat. Modifications of infant feeding practices aim to reduce HIV-1 transmission through breast milk; replacement feeding is neither affordable nor safe for the majority of African women, and early breast-feeding cessation (eg, prior to 6 months of life) requires substantial care and nutritional counseling to be practiced safely. The recent roll out of ARV treatment has changed the paradigm of prevention of MTCT. To date, postnatal ARV interventions that have been evaluated target either maternal ARV treatment to selected breast-feeding women, with good efficacy, or single-drug postexposure prophylaxis for short periods of time to their neonates, with a partial efficacy and at the expense of acquisition of drug-related viral resistance. We hypothesize that a viable solution to eliminate pediatric AIDS lies in the universal provision of fully suppressive ARV regimens to all HIV-1-infected women through pregnancy, delivery, and the entire breast-feeding period. On the basis of available evidence, we suggest translating into practice the recently available evidence on this matter without any further delay.