HIV infection and mortality rates in African children are astoundingly high. Risk factors for mother-to-child transmission of HIV include maternal plasma viral load and breastfeeding. With regard to the latter, current data indicate that mixed feeding (breastfeeding with other oral foods and liquids) is associated with the greatest risk of transmission. Studies are under way to determine if exclusive breastfeeding with rapid early weaning can reduce transmission rates in the absence of exclusive formula feeding for all infants. Perinatal transmission rates have been dramatically reduced with the use of single-dose nevirapine, but this strategy protects only approximately 50% of infants, and more than 75% of women receiving nevirapine develop a major nevirapine resistance mutation. In developed areas of the world, antiretroviral therapy has reduced perinatal transmission by more than 90% compared with 1993 rates. Improved HIV-related care for HIV-infected women in Africa is needed to reduce rates of HIV infection in children and to prevent maternal mortality. This article summarizes a presentation by Sten H. Vermund, MD, PhD, at the International AIDS Society-USA course in Chicago in May 2004.