In areas of the world where genital tract infections (GTIs) are common, the prevalence of HIV and the rate of mother-to-child transmission (MTCT) of HIV are also high. Although observational studies suggested that GTIs are associated with MTCT of HIV, no controlled clinical trial has confirmed this finding. It is likely that GTIs that cause either discharges or ulcers during pregnancy increase perinatal transmission of HIV. Several potential biological mechanisms might facilitate perinatal transmission. For example, chorioamnionitis, increased viral shedding in cervicovaginal secretions, increased HIV acquisition during pregnancy, inflammatory cytokine production, preterm labor, prolonged rupture of membranes, ascending infection, and increased intrapartum infectious secretions are factors that can be associated with GTIs. Several studies have shown that treating clinical conditions associated with inflammation might alter HIV shedding. It is conceivable that preventing ascending infection or reducing exposure of the infant to infectious material during birth could reduce MTCT. This can possibly be achieved by antimicrobial therapy during pregnancy and intrapartum. Such an approach is practical, is less expensive, and has secondary benefits related to prevention of adverse pregnancy outcomes associated with GTIs. Antibiotics might also complement reductions in MTCT of HIV obtained by antiretrovirals given to the mother around the time of delivery. In addition, antibiotics could reduce infectious causes of morbidity and mortality in infant and mother.