Arginine (2-amino-5-guanidino pentanoic acid) was shown in 1895 by Hedin to be present in the proteins of horn. Metabolic nitrogen balance studies, conducted in 1957 by Rose in human adults and in 1959 by Snyderman and coworkers in young infants, revealed that a dietary source of this amino acid was not an obligatory requirement for growth and maintenance of nitrogen homeostasis in healthy individuals. Hence, It was initially classified as a non-essential (dispensable) amino acid and, perhaps, for reasons of this classification arginine did not receivc the earlier atteniion it now deserves, in relation to an understanding of the nutritional biochemistry and physiology of its metabolism in humans subjects. However, there is currently a considerable interest in the cellular and tissue functions, as well as clinical, therapeutic significance, of arginine. In this paper we review the multiple functions of arginlne, including its role in the L-arginine-nitric oxide pathway,cellular regeneration, immune function, protein synthesis and protein breakdown. We then consider some in vivo aspects of the physiology of arginine metabolism, which varies greatly among eukaryotes, with particular reference to humans. Against this background, studies of arginine in the nutrition of humans under various pathophysiological conditions are reviewed briefly. Finally, a new, updated concept for the metabolic basis for the “conditional essentiality” of arginine is proposed Arginine (2-amino-5-guanidino pentanoic acid) was shown in 1895 by Hedin to be present in the proteins of horn. Metabolic nitrogen balance studies, conducted in 1957 by Rose in human adults and in 1959 by Snyderman and coworkers in young infants , revealed that a dietary source of this amino acid was not an obligatory requirement for growth and maintenance of nitrogen homeostasis in healthy individuals. Hence, It was initially classified as a non-essential (dispensable) amino acid and, perhaps, for reasons of this classification arginine did not receivc the earlier atteniion it now deserves, in relation to an understanding of the nutritional biochemistry and physiology of its metabolism in humans subjects. However, there is currently a considerable interest in the cellular and tissue functions, as well as clinical, therapeutic significance, of arginine. In this paper we review the multiple functions of arginlne, including its role in the L-arginine-nitric oxide pathway, cellular regeneratio tion; immune function, protein synthesis and protein breakdown. We then consider some in vivo aspects of the physiology of arginine metabolism, which vary greatly among eukaryotes, with particular reference to humans. Against this background, studies of arginine in the nutrition of humans under various, pathophysiological conditions are reviewed briefly. Finally, a new, updated concept for the metabolic basis for the “conditional essentiality ” of arginine is proposed