Necrotizing enterocolitis (NEC) is the leading cause of death and long-term disability from gastrointestinal disease in preterm infants, and is characterized by acute and chronic intestinal inflammation that may lead to systemic sepsis and multi-system organ failure. NEC typically develops in the preterm infant after the administration of tube feeds, although it may occasionally be seen in full-term babies. Despite extensive clinical experience in the management of patients with NEC, the underlying cellular and molecular mechanisms leading to its development remain incompletely understood. Several animal models have therefore been developed in a variety of species in order to study the pathogenesis of NEC and to develop more effective treatment strategies. This review seeks to examine the pros and cons of animal models that have been developed in the study of NEC over the past 30 years. It will highlight the various strengths and weaknesses of experimental approaches that have been used, and discuss potential directions for the development of such models for the future.