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Necrotizing enterocolitis (NEC) is a multifactorial disease that affects the small and large intestines, causing acute necrotic ischemia. It is the most common serious disease of the gastrointestinal (GI) system of premature infants, and in many cases it is fatal. It occurs mainly in premature infants, but can also affect full-term infants. Various unresolved issues, such as unproven pathogenesis, inadequate and often difficult therapy, and the lack of a commonly accepted and effective prevention strategy, make this disease an enigmatic clinical entity. With a prevalence of 7-14% in very low birth weight (VLBW) infants (i.e., 500-1,500 g) and a fatality rate approaching 20-50%, NEC continues to be a significant clinical problem. The frequency of occurrence and fatality of NEC are both inversely related with birth weight (BW) and gestational age (GA). The lack of appropriate preventive and therapeutic measures results in a significant proportion (20-40%) of infants with NEC undergoing surgery. In addition, 10-30% of NEC cases have significant morbidity, with digestive, neurological, visual and hearing problems. Despite systematic research, the predisposing factors and pathogenetic mechanisms of the disease have not yet been defined completely. Immaturity of the GI system because of prematurity, and LBW are the most significant risk factors for occurrence of NEC. The clinical picture of NEC is extremely wide and includes symptoms and signs from the GI and other systems. The diagnosis is based on the clinical pattern and results of radiological examination. The treatment of NEC includes medical intervention and surgery and the therapeutic choice depends mainly on the stage of disease. Prompt diagnosis and treatment of NEC have considerably decreased the mortality of the disease and the associated morbidity. Preventive measures for NEC include human milk, appropriate feeding and acidication of enteral feeding, and administration of prenatal corticosteroids to the mother, and enteral antibiotics, probiotics, prebiotics, arginine and erythropoietin to the infant. [ABSTRACT FROM AUTHOR]