Neonatal infections are a major cause of mortality and morbidity, with the majority of cases occurring in low- and middle-income countries, where high-risk household habits, poor care seeking and access to quality care, and poor health systems are prevalent. Infection surveillance is inadequate, but limited evidence suggests that antibiotic resistance is on the rise. However, there are numerous preventive and curative therapies that, if adopted properly on a global scale, might avoid the majority of neonatal fatalities caused by severe illnesses around the world. The development of new and modified methods and technologies has the potential to increase the availability and impact of interventions to prevent infections-related fatalities. However, implementation issues continue to limit intervention coverage. Evidence-based interventions must be delivered at the community level and in health facilities, and must be linked with maternal and child health initiatives.