This article reviews the epidemiology of perinatal (HIV)-1 in the United States in the past 2 decades and the international HIV epidemic among pregnant women and their infants. Since the peak of 1700 reported cases of pediatric AIDS in 1992, there has been dramatic progress in decreasing perinatal HIV transmission in the United States with fewer than 50 new cases of AIDS annually (>96% reduction) and fewer than 300 annual perinatal HIV transmissions in 2005. This success has been due to use of combination antiretrovirals given to mothers during pregnancy and labor/delivery, obstetric interventions that reduce the risk of transmission, provision of zidovudine (ZDV) prophylaxis for 6 weeks to HIV-exposed newborns and use of formula. Internationally, the burden of mother-to-child HIV transmission remains heavy with 2.1 million children less than 15 years of age estimated to be living with HIV and 430,000 new HIV infections in infants occurring each year, with most cases occurring in Africa. Current international efforts are directed at scaling up successful prevention of mother-to-child transmission interventions and new research directed at making breastfeeding safer using antiretroviral prophylaxis to either mothers or their infants.