Neonatal bacterial infection is a significant cause of morbidity and mortality despite improved survival of premature newborns, better understanding of the pathophysiology of sepsis, advances in supportive care, and more potent antibacterial agents. Early recognition and implementation of appropriate therapy offers the best outcome, and careful assessment of the newborn is essential. Current methods to detect signs of sepsis and to identify the causative microorganism are not 100% sensitive and precise. Continued research on other indicators may yield better diagnostic methods and therapy in the future. Research is necessary to identify the most sensitive markers for diagnosis of sepsis and methods of immune enhancement that are safe and effective.