OBJECTIVE: Our objective was to determine the potential for chlorhexidine used as a vaginal and neonatal wash to reduce adverse outcomes of pregnancy, especially in developing countries. DATA SOURCES: We searched the English literature from January 1950 through October 2005 for all articles related to the use of chlorhexidine. METHODS OF STUDY SELECTION: Every article on chlorhexidine use in pregnancy and in the newborn period was reviewed in detail. The results of every study in which chlorhexidine was used as a vaginal treatment, with or without a neonatal wash, for all pregnancy outcomes except mother-to-child transmission of human immunodeficiency virus, are summarized in this review. TABULATION, INTEGRATION AND RESULTS: Chlorhexidine is a highly effective killer of most bacteria, has an excellent safety profile, rarely is associated with bacterial resistance, is easy to administer, and costs a few cents per application. When used as a vaginal or newborn disinfectant, it clearly reduces bacterial load, including transmission of Group B Streptococcus from the mother to the fetus. Nevertheless, in developed countries, chlorhexidine generally has not been shown to significantly reduce life-threatening maternal or neonatal infections. However, 2 large but not randomized studies, one in Malawi and the other in Egypt, suggest that important reductions in maternal and neonatal sepsis and neonatal mortality may be achievable with vaginal or neonatal chlorhexidine treatment. CONCLUSION: With 4 million neonates and about 700,000 pregnant or recently pregnant women-mostly in developing countries-dying each year, many from infections originating in the vagina, further study of this highly promising treatment is indicated.