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Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in preterm infants and continues to be a major cause of morbidity and mortality. The incidence of NEC as well as mortality from the disease has persisted at unacceptably high levels for decades as current understanding of the cause remains incomplete. Identifying infants at risk and preventing NEC are mainstays of care. This article briefly examines disease presentation and treatment, identifies gaps in current understanding of disease pathology, and highlights new research that may lead to a decrease in the incidence of NEC in the future.