The other speakers at this symposium will consider some of the detailed properties of glucose-6-phosphate dehydrogenase and the special role of this enzyme in the metabolism of the red cell. In order to set the stage for this discussion, I will attempt to provide a brief review of the historic background of the subject and some of our current thinking regarding the role of the hexosemonophosphate pathway, sometimes known as the pentose phosphate pathway, in the over-all economy of the cell. Particular attention will be given to the relation of the pentose phosphate pathway to the glycolytic, or EmbdenMeyerhof, pathway. Perhaps the best way to gain some understanding of the role of each of the two majorpathways is through a consideration of the specific functions of the pyridine nucleotide coenzymes. Almost all living cells contain two pyridine nucleotides, diphosphopyridine nucleotide (DPN) and triphosphopyridine nucleotide (TPN), each of which functions with its own group of substrates in a highly specific manner. Why should there be a need for two such similar coenzymes in the same cell? The answer to this question provides the key to the function of the several pathways of carbohydrate metabolism. It is of particular interest to examine the function of the pyridine nucleotides in the light of their original discovery. DPN was discovered in 1906 by Harden and Young as the coenzyme of alcoholic fermentation in yeast (Fig. 1). A number of years later it was shown by Meyerhof to be required for the conversion of glucose to lactic acid in muscle. Thus, from its very discovery, DPN was considered to be the coenzyme of fermentation. On the other hand, TPN was discovered by Warburg and associates as the coenzyme for the oxidation of glucose-6-phosphate to 6-phosphogluconate (Fig. 2). Later it was shown by Warburg and Christian to be required for the next step as