In healthy adult humans, eight amino acids (isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine) were shown classically by nitrogen balance studies to be indispensable. Subsequent studies classifying histidine as indispensable are reviewed in this article. We also review the evidence that in certain nutritional or disease states or in certain stages of development otherwise dispensable amino acids may become indispensable. Arginine, citrulline, ornithine, cysteine, and tyrosine thus may be considered as acquired indispensable amino acids. Evidence for the indispensability of taurine is also considered. We propose a classification of the indispensability of amino acids based on clinical and therapeutic considerations.