Necrotizing enterocolitis is a devastating disease of newborns associated with intestinal inflammation and necrosis. In spite of advances in neonatal care, intensive care units and refinement of surgical practices, the high mortality and long term morbidity due to NEC remains a challenge. The pathogenesis of the disease is complicated and not completely understood. Gradual development in the field of NEC revealed innate immune system, comprised of 'Toll-like receptors' (TLR) in the pathogenesis of the disease. TLR4 is an important member of TLR and is the receptor for bacterial lipopolysaccharide. Activation of TLR4 causes intestinal mucosal injury and decreased epithelial repair in premature neonates. Probiotics are live microorganisms and are rich in bacterial DNA. CpG motifs of DNA can inhibit TLR4 signaling and reduce NEC severity. Probiotics also modulate enterocyte genes that regulate innate immune-mediated inflammation, thereby preventing NEC. The above molecular basis is supported by multiple individual studies using probiotics especially Lactobacillus and Bifidobacteria for preventing NEC in preterm infants. Their encouraging results prompted us to carry out an analysis of major trials on probiotics along with considering pathophysiological and immunological aspects of the disease. Prebiotics have a protective effect in NEC by stimulating colonization of beneficial bacteria in intestine. Products containing both probiotics and prebiotics (synbiotics) were also tried and they are found to be more beneficial than either probiotics or prebiotics. This review will highlight recent concepts and evidences on probiotics and prebiotics in preventing NEC in preterm, low birth weight infants.