The advent of highly active antiretroviral therapy has facilitated the virtual elimination of mother-to-child transmission of HIV infection in developed countries, reducing transmission rates to approximately 1 to 2%. In these settings, highly active antiretroviral therapy has also transformed pediatric HIV infection into a chronic disease; although there are associated costs in terms of side effects and the heavy pill burden. In less developed settings, easier-to-use adaptations of antiretroviral therapy regimens, such as short-course and single-dose antiretroviral strategies or neonatal postexposure prophylaxis can also substantially prevent mother-to-child transmission, although to a lesser degree than highly active antiretroviral therapy. However, postnatal transmission of infection through breastfeeding significantly reduces the longer-term efficacy of these strategies. Ongoing research is focusing on the use of antiretroviral therapy in the breastfeeding period.