This Review will describe the current experimental models available for the study of NEC and their role in elucidating the important role of toll-like receptor 4 (TLR4) in disease pathogenesis, and will consider the key opportunities for research in the NEC field and how these may be best answered through precision-based models including the novel NEC-in-a-dish approach. This evidence concerns the gene TLR4 and necrotizing enterocolitis.