The intestine serves numerous purposes. In addition to digestion and absorption, the intestine functions as an organ that provides specific and nonspecific protection against pathological bacteria and noxious agents. At birth, and certainly when birth occurs prematurely, these functions are not yet fully developed. This article addresses the specific needs of the neonatal gut to perform these functions adequately and describes efforts to modulate intestinal barrier function by preterm formula supplemented with insulin-like growth factor 1.