Ten years after the first trials demonstrating the efficacy of zidovudine (ZDV) for the prevention of mother-to-child transmission (pMTCT) of HIV, different antiretroviral approaches have been validated in resource-limited settings. Remarkable progress has been made in the last 4 years, with trials demonstrating the efficacy of postexposure antiretroviral prophylaxis in Malawi, as well as studies in Thailand and Côte d'Ivoire assessing the efficacy and viral resistance patterns of short-course regimens combining ZDV plus single-dose nevirapine (sdNVP). The field efficacy of a short course of ZDV plus lamivudine (3TC), together with sdNVP, has also been recently reported, with 6-week transmission rates below 5% for the first time in Africa in a population in which 40% breast-feed. The introduction of HAART for pregnant women has begun on a small scale in resource-limited settings and will hopefully further reduce transmission. What remains is the crucial issue of viral resistance after antiretroviral therapy for pMTCT, especially in the context of the growing availability and use of sdNVP in national pMTCT programs. Preliminary data from South Africa and Côte d'Ivoire suggest that the maternal use of ZDV plus 3TC for at least 3 days postpartum may reduce the occurrence of resistance mutations after maternal exposure to sdNVP. In the context of increasing controversy surrounding the use of sdNVP for pMTCT, the World Health Organization has recently reiterate its recommendations for its use for pMTCT in resource-constrained settings within a wide panel of antiretroviral regimens, in order to allow greater and quicker population coverage. The field application of pMTCT study results is a real challenge, and innovative approaches need to be designed an evaluated ot increase uptake of pMTCT programs in resource-poor settings. Research must continue to identify new interventions and new antiretroviral drugs for pMTCT.