Despite the use of highly active antiretroviral therapy (HAART) and the success of protocol PACTG-076 in decreasing perinatal transmission of HIV infection in many industrialized countries, a total of 5,600,000 new cases of HIV infection were diagnosed worldwide in 1999. Of those cases, more than 10% are children under 15 years of age. The vast majority of pediatric HIV infection is due to perinatal transmission. More than 95% of HIV-infected people live in the developing world. Different studies are currently being conducted with modifications of the original PACTG-076, especially shorter courses of zidovudine (ZDV), combinations of antiretrovirals (ZDV and 3TC), or comparison of a modified version of the standard ZDV course vs. a single dose of nevirapine for the mother intrapartum and also for the newborn. The results of these studies may provide more affordable, alternative regimens to prevent maternal-to-child HIV-1 transmission for developing countries than the PACTG-076 protocol. It is very important that physicians and physician extenders (nurse practitioners and physician assistants) caring for infants born to HIV-infected mothers have an understanding of the pathophysiology of vertical HIV-1 infection transmission. They should be familiar with the conditions associated with an increased risk of transmission, interventions available to decrease this risk, current medications, and laboratory resources.