Amino acids function as precursors for de novo protein synthesis. In addition, however, they play a key role as nutritional signals that regulate multiple cellular processes. There is ample in vitro and in vivo evidence showing that muscle tissue responds to increases in amino acid availability via signal transduction pathways that are also regulated by insulin, glucagon, growth hormone, and insulin growth factor 1. The increased amino acid availibility results in the upregulation of mRNA translation, thereby increasing muscle protein synthesis, which, in turn, leads to greater net muscle protein accretion. These findings have been particularly pronounced for the amino acid leucine. Furthermore, leucine has the ability to act as a strong insulin secretagogue. Consequently, it has been suggested that leucine represents an effective pharmaconutrient for the prevention and treatment of sarcopenia and type 2 diabetes. In accordance, recent in vivo studies in humans show that free leucine ingestion can reverse the blunted response of muscle protein synthesis to amino acid/protein intake in the elderly. Although short-term studies suggest that leucine supplementation can stimulate muscle mass accretion in the elderly, there are no long-term nutritional intervention studies to confirm this or the other proposed benefits of leucine as a pharmaconutrient.