Worldwide, more than 1600 infants become infected with HIV each day. Almost all infections are a result of mother-to-child transmission of HIV, with most of these infections occurring in resource-poor countries. In developed countries, antiretroviral prophylaxis has dramatically reduced perinatal transmission to <2%. The potential now exists to extend this success to resource-poor countries using effective but shorter and less expensive antiretroviral regimens. With the potential widespread use of antiretroviral therapy for perinatal HIV prevention in resource-limited settings, there will be exposure of increasing numbers of infants to in utero and postpartum antiretroviral drugs for which long-term toxicity data is unknown. This article focuses on a review of what is known about safety of antiretroviral regimens used to interrupt mother-to-child transmission for women and their children.