Necrotizing enterocolitis remains a common cause of morbidity and mortality in the neonatal period. Despite many advances in the management of the critically ill neonate, the exact etiology, attempts at prevention and determining best treatment for NEC have been elusive. Unfortunately, the overall survival for this poorly understood and complex condition has not improved. NEC is a condition that can and should be studied with randomized prospective trials (RCTs). This chapter reviews the current evidence-based trials for this condition thus far performed.