Group B Streptococcus (GBS) is an important cause of neonatal sepsis in term and preterm infants. Because GBS colonizes human genitourinary and gastrointestinal tracts, a significant focus of neonatal GBS disease prevention is to interrupt vertical transmission of GBS from mother to infant during parturition. Routine antepartum GBS screening in pregnant women, as well as widespread use of intrapartum antibiotic prophylaxis, have aided in overall reductions in neonatal GBS disease during the past 3 decades. However, neonatal GBS disease persists and may cause mortality and significant short- and long-term morbidity among survivors. Herein, we highlight contemporary epidemiology, microbial pathogenesis, and the clinical presentation spectrum associated with neonatal GBS disease. We summarize obstetric recommendations for antenatal GBS screening, indications for intrapartum antibiotic prophylaxis, and considerations for antibiotic selection. Finally, we review national guidelines for risk assessment and management of infants at risk for GBS disease.