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Group B streptococcal infection is the most common cause of neonatal sepsis and is responsible for significant neonatal morbidity and mortality. Group B streptococcus is also the causative agent in 50,000 maternal infections per year. Approximately 30% of women have asymptomatic group B streptococcal colonization at some time during pregnancy, but the neonatal attack rate is only about 2 per 1,000 deliveries. Maternal and neonatal risk factors contribute to the rates of vertical transmission and symptomatic neonatal disease. Options that have been investigated for prevention of neonatal group B streptococcal disease include identification of at-risk pregnancies as well as antenatal, intrapartum, and neonatal treatment. The intrapartum treatment of women at risk for vertical transmission of group B streptococcus to their neonates unequivocally has been shown to decrease the rate of neonatal colonization. Practitioners should implement one of two strategies that incorporate intrapartum prophylaxis for prevention of perinatal group B disease.