Necrotizing enterocolitis (NEC) remains among the most common and devastating diseases in neonates. Despite advances in neonatal clinical care, specific treatment strategies and diagnostic modalities remain lacking. As a result, morbidity and mortality remain high. Improved understanding of the pathogenesis of NEC has the potential for improved therapeutics. Some of the areas of research leading to promising discoveries include inhibition of Toll-like receptor signaling, modulation of vascular endothelial growth factor signal pathways, defining metabolomic alterations in NEC to discover potential biomarkers, probing for genetic predispositions to NEC susceptibility, determining mechanistic relations between anemia and NEC, and microflora modulation through the use of probiotics. All of these areas may represent novel promising approaches to the prevention and treatment of NEC. This review will focus on these current and possible therapeutic perspectives.