Necrotising enterocolitis (NEC) continues to have significant mortality, and morbidity including neurodevelopmental impairment, especially in extreme preterm neonates needing surgery for the illness. The incidence of NEC has not changed significantly despite the advances in neonatal care. Preventing NEC thus remains a priority. Protecting the intestinal barrier function and controlling the excessive proinflammatory response by the preterm gut are perhaps the most important areas for research toward achieving this goal. Improved understanding of the role of innate immunity in the pathogenesis of the illness and progress in other areas means that novel strategies may become available for the prevention and treatment of NEC. Probiotics significantly reduce the risk of NEC. Evidence indicates that bovine lactoferrin could reduce both, sepsis and NEC. As new frontiers (e.g. oral erythropoietin, heparin binding epithelial growth factor, therapeutic hypothermia and stem cell therapy) are being explored, the benefits of antenatal glucocorticoids, breast milk and standardised feeding regimes must not be forgotten. Preventing sepsis and avoiding undue prolonged exposure to antibiotics and antacids will be equally important. Considering the multiple complex pathways involved in its pathogenesis, adopting a package of potentially better practices will be the most appropriate strategy for prevention and treatment of NEC.