Severe thrombocytopenia (< 50 x 10(9)/L) frequently accompanies advanced necrotizing enterocolitis (NEC). In premature infants with severe thrombocytopenia, despite a paucity of evidence to support the practice, platelet transfusions are commonly used to maintain arbitrary levels of platelet counts in an effort to prevent hemorrhage. However, platelet transfusions contain a variety of bioactive factors, including platelet activating factor (PAF), which can augment systemic inflammatory processes. A growing body of evidence that incriminates PAF in the pathogenesis of NEC has emerged over the past few decades from both animal and human data. Both severe thrombocytopenia and multiple platelet transfusions have been associated with increased mortality, but it is admittedly difficult to differentiate between the effects of the underlying disease and the effects, if any, of the platelet transfusions. In this report, we review the roles of PAF and platelet transfusions in infants with severe NEC.