Necrotizing enterocolitis (NEC) is an important neonatal disease with a high mortality rate. The pathophysiology is unclear but epidemiologic studies suggest that hypoxia and infection are important risk factors. In this review we discuss the effect of hypoxia and platelet-activating factor (PAF) on intestinal blood flow and intestinal necrosis, and implicate PAF as an important mediator in hypoxia-induced intestinal injury. Finally we provide evidence that PAF may be important in neonatal NEC.