GI trophic factors that influence the coordinated pre- and postnatal growth and development of the GI tract have been identified. Studies in animals and humans demonstrate that GI trophic factors can initiate cellular growth and expression of differentiated function, and they are important in adaptation and repair following injury. Systemically as well as enterally administered growth factors can stimulate GI growth and maturation, suggesting that trophic factors in the serum of neonates may modulate GI growth via receptors on the serosal membranes of enterocytes. GI trophic factors may be synthesized endogenously or provided postnatally in milk. GI trophic factors in human milk play an important role in regulating the adaptive functional changes that accompany the transition to postnatal enteral feedings. Although human milk growth factors do not appear to be essential for infant survival, the elevated risk of gastrointestinal-related illnesses in formula-fed as compared with breast-fed infants (diarrhea, necrotizing enterocolitis, colitis, Crohn's disease) suggest that bioactive compounds in human milk contribute to the apparent protective effect of breast feeding. GI trophic factors have the potential to be used therapeutically to enhance GI maturation and repair following injury. These applications may be particularly useful in the premature or postsurgical infant. Several issues require further research, including (1) the mechanism of action, (2) the efficacy of oral versus systemic administration, (3) characterization of the complex interactions between the various growth factors, because some appear to act synergistically, (4) the effect of exogenously administered growth factors on endogenous production of that factor, its receptor, or other growth factors, (5) the effect of growth factors upon tissues not directly associated with the GI tract, and (6) the determination of safe and effective upper limits.