Group B *Streptococcus* (GBS) is a significant cause of neonatal sepsis, affecting both term and preterm infants. The primary focus of prevention is to interrupt vertical transmission from mother to infant during childbirth. Routine antepartum GBS screening and intrapartum antibiotic prophylaxis (IAP) have significantly reduced the incidence of early-onset GBS disease (EOGBS) over the past three decades. However, EOGBS remains a concern, with an estimated incidence of 0.2 cases per 1000 live births in the U.S. in 2020. Late-onset GBS disease (LOGBS) has stable incidence, with an estimated 0.3-0.4 cases per 1000 live births, and accounts for 57% of all neonatal GBS cases. Preterm infants are at higher risk for both EOGBS and LOGBS, with mortality rates of 19% and 8%, respectively. Maternal GBS colonization is a major risk factor, and IAP is indicated for all parturients with positive screening results. Penicillin and ampicillin are the preferred agents for IAP, given their effectiveness and low resistance rates. Risk assessment for EOGBS includes clinical status, maternal intrapartum fever, and exposure to appropriate IAP. Empiric antibiotic regimens for infants at risk of EOGBS include ampicillin and an aminoglycoside. Management of confirmed infections involves narrowing antibiotics based on susceptibility testing. Neurodevelopmental impairment is a significant long-term complication, affecting 32% of survivors of neonatal GBS meningitis. Efforts to develop a maternal GBS vaccine are ongoing to further reduce the burden of GBS disease.Group B *Streptococcus* (GBS) is a significant cause of neonatal sepsis, affecting both term and preterm infants. The primary focus of prevention is to interrupt vertical transmission from mother to infant during childbirth. Routine antepartum GBS screening and intrapartum antibiotic prophylaxis (IAP) have significantly reduced the incidence of early-onset GBS disease (EOGBS) over the past three decades. However, EOGBS remains a concern, with an estimated incidence of 0.2 cases per 1000 live births in the U.S. in 2020. Late-onset GBS disease (LOGBS) has stable incidence, with an estimated 0.3-0.4 cases per 1000 live births, and accounts for 57% of all neonatal GBS cases. Preterm infants are at higher risk for both EOGBS and LOGBS, with mortality rates of 19% and 8%, respectively. Maternal GBS colonization is a major risk factor, and IAP is indicated for all parturients with positive screening results. Penicillin and ampicillin are the preferred agents for IAP, given their effectiveness and low resistance rates. Risk assessment for EOGBS includes clinical status, maternal intrapartum fever, and exposure to appropriate IAP. Empiric antibiotic regimens for infants at risk of EOGBS include ampicillin and an aminoglycoside. Management of confirmed infections involves narrowing antibiotics based on susceptibility testing. Neurodevelopmental impairment is a significant long-term complication, affecting 32% of survivors of neonatal GBS meningitis. Efforts to develop a maternal GBS vaccine are ongoing to further reduce the burden of GBS disease.