Acute hyperglycemia is associated with excess morbidity and mortality in acute cardiovascular illness in both diabetic and nondiabetic patients. Hyperglycemia is associated with altered myocardial energetics, but abnormalities in glucose oxidation and glycolysis do not fully account for this excess risk. Hyperglycemia leads to a pro-oxidative/ proinflammatory state that is associated with endothelial dysfunction, diminished coronary vasodilatory reserve, and a prothrombotic state. Hyperglycemia negates the protective effect of ischemic preconditioning and, most importantly, appears to interfere with the salutary effects of insulin in acute cardiovascular illness. Aggressive therapy with continuous infusion of insulin seems to improve a host of metabolic and physiologic effects associated with acute hyperglycemia and appears warranted if euglycemia can be maintained.