The fear of necrotizing enterocolitis and feeding intolerance are major factors inhibiting the use of the enteral route as the primary means of nourishing premature infants. Parenteral nutrition may help to meet many of the nutritional needs of these infants, but has significant detrimental side effects that include intestinal atrophy, sepsis, and increased susceptibility to inflammatory stimuli and systemic inflammatory responses. Being able to minimize the use of the parenteral route and still maintain appropriate nutrition safely would be a major advance in neonatology. At the basis of our inability to use the enteral route is a poorly understood immature gastrointestinal tract. Approaches such as minimal enteral nutrition or trophic feedings may partially alleviate these problems. However, if we are to progress in greater utilization of the gastrointestinal tract, other factors need to be considered. These include the macronutrient composition of minimal enteral or trophic feedings and the microecology of the intestinal lumen. Some of the developmental aspects of the intestine, which include intestinal growth, motor activity, barrier and other innate immune functions, and the microecology of the developing intestine, are briefly reviewed here. The purpose of this review is to suggest important areas of future research in neonatal and developmental gastroenterology that could affect several conditions that are related to immaturity of the gastrointestinal tract. Am J Clin Nutr 2007;85(suppl):629S-34S.