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Long-term, sustainable programs to address high incidence and death rates from neonatal infections are required for improving child survival. There is an urgent need to define the role of community-based management for neonates with serious bacterial infections—-both at home and at first-level facilities.We reviewed available evidence for community-based antibiotic management strategies for serious neonatal infections.Nine distinct studies contributing data for community-based management of neonatal pneumonia and sepsis were identified. In a pooled analysis of 5 controlled trials of community-based management of neonatal pneumonia (4 using cotrimoxazole, 1 ampicillin, or penicillin), all-cause neonatal mortality showed 27% [95% confidence interval (CI): 18%–35%] reduction and pneumonia-specific mortality, 42% (95% CI: 22%–57%). Substantial reductions in neonatal mortality have been demonstrated in a nonrandomized controlled study in rural India (62% reduction, P < 0.001) and in a cluster randomized trial in rural Bangladesh (34% reduction, 95% CI: 7%–53%). Reduced case fatalities (0%–3%) with community-based management of neonatal sepsis were observed in 2 small uncontrolled studies from India and Guatemala and a recent randomized trial from Pakistan.Although methodological limitations preclude estimating the precise contribution of antibiotics toward neonatal mortality reduction in community settings in low income countries, available data suggest substantial benefit of case management approaches using antibiotics for neonatal sepsis in such settings.