In recent years, human immunodeficiency virus (HIV) infection has emerged as a leading cause of death among young children, most of whom acquired their infection perinatally. Without effective prevention efforts, transmission of HIV through heterosexual sex will continue to increase among women, and the number of perinatally infected children will mirror this increase. In 1994, researchers at the National Institutes of Health and its collaborators announced results from a randomized clinical trial indicating that zidovudine therapy administered to a select group of HIV-infected pregnant women and their newborns reduced the risk of perinatal transmission by two-thirds. This article reviews this clinical trial and its significant findings, discusses the ensuing recommendations from the US Public Health Service, discusses their implications for prenatal counseling and testing, and describes future research needs.