In the past thirty years a vast body of information has been compiled relating to carbohydrate metabolism. Nevertheless, it is becoming increasingly evident that the elucidation of the metabolic disturbance in diabetes mellitus requires an even more complete knowledge than is presently available of the complex chemical routes followed by glucose in its conversions and interactions with other cell components. In this area of carbohydrate metabolism most gratifying progress has been made with the demonstration of previously unsuspected pathways of glucose utilization. Until rather recently, it was generally believed that the primary, if not the sole, route of glucose breakdown by mammalian tissue was via the Embden-Meyerhof or anaerobic-glycolytic pathway involving the conversion of glucose to pyruvate and lactate and its subsequent oxidation to co2 by the citric acid cycle. Evidence has now accumulated to indicate the existence of at least one new pathway of glucose metabolism, referred to as the pentose phosphate pathway, or the hexose monophosphate oxidative shunt, which may often supplement significantly the anaerobic-glycolytic scheme. Before turning to some of the details and possible significance of this alternate pathway, a brief review of the reactions of glycolysis and the citric acid cycle is desirable.