Sepsis-related morbidity and mortality are increasing concerns in all Neonatal Intensive Care Units, with reported incidences that are dramatically high regardless of the improvements in the quality of neonatal assistance. Preterm neonates display clinical characteristics that make them prone to infections. Neonatal sepsis is one of the major causes of neonatal death in developing countries. Different microorganisms are responsible for disease according to the age at onset. Simple preventive and treatment strategies have the potential to save many newborns from sepsis-related death. This article is a review for understanding issues related to sepsis in the neonatal intensive care unit.