Necrotizing enterocolitis, a potentially fatal intestinal inflammatory disorder affecting primarily premature infants, is a significant cause of morbidity and mortality in neonates. While the etiology of the disease is, as yet, unknown, a number of risk factors for the development of necrotizing enterocolitis have been identified. One such risk factor, formula feeding, has been shown to contribute to both increased incidence and severity of the disease. The protective influences afforded by breastfeeding are likely attributable to the unique composition of human milk, an extremely potent, biologically active fluid. This review brings together knowledge on the pathogenesis of necrotizing enterocolitis and current thinking on the instrumental role of one of the more prominent classes of bioactive components in human breast milk, glycosaminoglycans.