Invasive disease due to group B Streptococcus infection (Streptococcus agalactiae) results in a wide spectrum of clinical disease. In North America, serotypes Ia, Ib, II, III, and V are most frequently associated with invasive disease. Group B Streptococcus remains a continuing source of morbidity and mortality in high-risk populations, including pregnant women, neonates, and the elderly; an increasing incidence of invasive disease has been observed in nonpregnant adults. Group B Streptococcus remains the most common culture-confirmed neonatal bacterial infection in the United States and is a significant source of neonatal morbidity globally. Intrapartum antibiotic prophylaxis has reduced the incidence of early-onset neonatal disease without a notable impact on the incidence of late-onset neonatal disease. Penicillin G remains the mainstay of therapy, although reduced penicillin susceptibility has been observed in select isolates. Increased frequency of resistance to non-beta-lactam antibiotics, including clindamycin, erythromycin, and fluoroquinolones, has been observed, with some isolates demonstrating resistance to vancomycin. The development and implementation of strategies to identify hosts, treat judiciously with antimicrobials with the narrowest spectra, and prevent invasive disease, with vaccines, are essential to reduce the burden of group B Streptococcus disease.