Publisher Summary Lipoic acid was discovered independently in several laboratories in the late 1940's as a growth factor and requirement for pyruvate oxidation for certain microorganisms. The trivial names “acetate-replacing factor”, “pyruvate oxidation factor”, “protogen”, and “B. R. factor” were used to designate the biologically active substance prior to its isolation and identification. It is interesting to note that within a period of about six years following the discovery of lipoic acid, this substancc, was isolated and characterized and the basic features of its site and mode of action were established. Lipoic acid has been shown to be widely distributed among microorgsnisms, plants, arid animals. Most nutritional investigations with higher animlas have failed to show a growth response to added lipoic acid. However, there is no doubt that this substance plays a vital role in animal metabolism. Thus far, the only well-defined role of lipoic acid is that of a Prosthetic group in multienzyme complexes that catalyze an oxidative decnrhoxylation of pyruvatc and α-ketoglutarate to produce acetyl coenzyme A (CoA) and succinyl CoA, respectively, and reduced diphosphopyridine nucleotide (DPNH). The purpose of this chapter is to evaluate and organize these data with a view to presenting an integrated picture in terms of reaction mechanisms of lipoic acid function in a-keto acid oxidation. Brief consideration is given to those aspects of the chemistry of lipoic acid that are deemed pertinent to its biological role.