Neonatal sepsis remains one of the most common and potentially preventable causes of mortality and long-term morbidity in the world. Although associated mortality is decreasing, over 400,000 neonates worldwide died from sepsis and other infectious conditions in 2015.1 Compared with uninfected infants, those who develop infections in the neonatal period are significantly more likely to have adverse neurodevelopmental outcomes at follow-up. These include cerebral palsy, poor vision, delayed psychomotor development, low Bayley Scales of Infant Development II scores on the mental development index, as well as impaired head growth, a known predictor of poor neurodevelopmental outcome.2 This chapter will examine the definition, epidemiology, pathophysiology, diagnosis, management, and outcome of neonatal sepsis.