Evidence is reviewed that favors the hypothesis that maintenance of glycolysis plays a special role in protecting membrane function in ischemia. Therefore all procedures stimulating glycolytic flux should be beneficial in ischemia, and procedures inhibiting flux should be harmful. However, a crucial consideration is the coronary flow rate. In severe ischemia, accumulation of protons, derived not directly from glycolytic flux but from the breakdown of ATP and from protonproducing cycles, will tend to inhibit glycolysis and to minimize any benefit from increased glycolytic flux. Therefore maintenance of intracellular pH is crucial to the concept of the benefits of glycolysis. It also follows that the severity of ischemia can determine whether or not enhanced glycolysis has a beneficial effect. It is argued that a multiple approach, including enhanced glycolytic flux, control of intracellular pH, and improved coronary flow, constitutes the combination most likely to benefit ischemia.