Necrotizing enterocolitis (NEC) has widespread implications for neonates. While mostly affecting preterm neonates, full-term neonates, especially those with congenital heart disease, are also at risk. Although the exact pathogenesis of NEC remains elusive, three major factors, a pathogenic organism, enteral feedings, and bowel compromise, coalesce in at-risk neonates to produce bowel injury. Initiation of the inflammatory cascade likely serves as a common pathway for the disorder. Clinical signs and symptoms range from mild feeding intolerance with abdominal distension to catastrophic disease with bowel perforation, peritonitis, and cardiovascular collapse. Vigilant assessment of at-risk neonates is crucial. When conservative medical management fails to halt injury, surgical intervention is often needed. Strategies to decrease the incidence and ultimately prevent NEC loom on the horizon, such as exclusive use of human breastmilk for enteral feedings and administration of probiotics.