Arginine functions in the body as a free amino acid, a component of most proteins, and the substrate for several non-protein, nitrogen-containing compounds, many of which function in immunity. Although arginine is synthesized in the body, it is not made in sufficient quantities to support growth or meet metabolic requirements during periods of stress. Based on the biochemical and physiological role of arginine in maintaining health and immunity, arginine is being added at pharmacologic concentrations to enteral formulas to boost immune function. Unfortunately, animal and human studies that investigate enteral arginine supplementation as the single variable do not show clear immunologic benefit. The inconsistent effects of arginine supplementation on immune function are due to numerous factors, such as the amount and timing of arginine supplementation, the animal species or strain of species, and the experimental model. Systematic study is required to determine whether a basal dietary intake of arginine is required to maintain immune function during health and how much arginine is required to meet metabolic requirements during periods of growth or stress.