Strategies to prevent infant group B streptococcal (GBS) disease, which results in approximately 400,000 cases and 90,000 deaths annually worldwide, vary by setting and evolve as new evidence and interventions become available. The primary proven intervention is intrapartum intravenous antibiotic prophylaxis (IAP) for prevention of GBS disease in the first week of life (early-onset, EOD). Under this strategy, at-risk women are identified based on late antenatal microbiologic screening for GBS colonization or presentation during labor with specific obstetric risk factors. Effectiveness of adequate IAP is high (>90% against EOD) but limitations include that IAP does not prevent disease after the first week of life (late-onset, LOD) and that it risks selection of antimicrobial resistance and disruption of the newborn microbiome. Because of the complexity and resource intensity of this strategy it is feasible mainly in high income countries. Simpler alternatives, including oral azithromycin and chlorhexidine vaginal washes, have not been found effective. Maternal GBS vaccine and associated transplacental transfer of antibodies to the infant offers an alternate potential prevention pathway that may protect against EOD and LOD with broad feasibility worldwide. Sero-epidemiologic evidence of antibody protection against infant GBS disease is accruing and at least 2 different vaccine products are in phase 2 development and anticipated to enter into phase 3 licensure trials. This keynote will review the pros and cons of IAP, the accruing epidemiologic evidence for antibody protection against infant GBS disease, and the opportunities a maternal GBS vaccine, alone or in combination with IAP, may afford.