Approximately 10% of infants born in the United States are of low birth weight. Growth failure during the neonatal period is a common occurrence in low birth weight infants due to their inability to tolerate full feeds, concerns about advancing protein supply, and high nutrient requirements for growth. An improved understanding of the nutritional regulation of growth during this critical period of postnatal growth is vital for the development of strategies to improve lean gain. Past studies with animal models have demonstrated that muscle protein synthesis is increased substantially following a meal and that this increase is due to the postprandial rise in amino acids as well as insulin. Both amino acids and insulin act independently to stimulate protein synthesis in a mammalian target of rapamycin-dependent manner. Further studies have elucidated that leucine, in particular, and its metabolites, α-ketoisocaproic acid and β-hydroxy-β-methylbutyrate, have unique anabolic properties. Supplementation with leucine, provided either parenterally or enterally, has been shown to enhance muscle protein synthesis in neonatal pigs, making it an ideal candidate for stimulating growth of low birth weight infants.