Necrotizing enterocolitis (NEC) is the most common surgical emergency in the neonatal intensive care unit and remains a major cause of death in neonates. Although the pathophysiology of NEC has not been completely elucidated, progress has been made in the characterization of the molecular events which may take place during an episode of ischemia. This possible initiating event is followed by a complex cascade of inflammatory mediators active in NEC: epidermal growth factor, platelet-activating factor, and, nitric oxide. Additionally, unique characteristics of the premature gut are thought to be crucial to the development of NEC. The diagnosis of NEC continues to be based on clinical and radiographic features. Several new laboratory tests are under investigation for the purposes of earlier diagnosis, but none have prevailed at this time. Both exploratory laparotomy, with intestinal resection and peritoneal drainage are widely practiced. Mortality rates remain high and have improved little over the last couple of decades. Therefore, prevention remains crucial in order to decrease the incidence of NEC. Cautious feeding regimens, the use of maternal breast milk, passive immunization, and the use of probiotics have all been suggested but not proven as possible preventive methods. Although many advances have been made, significant opportunity remains to improve our understanding of the disease process and to develop better strategies for prevention and treatment.