Diabetes mellitus is associated with increased risk for cardiovascular mortality because of multiple pathophysiologic mechanisms. Acute stress-induced hyper-glycemia during acute myocardial infarction has gained much attention, as blood glucose levels seem to be an independent risk factor for acute myocardial infarction-related death. Clinical studies that identify stress-induced hyperglycemia as a risk factor are reviewed and its causes are discussed. They can be summarized as the consequence of acute insulin resistance, which in its turn is caused by stress hormones and by proinflammatory cytokines. Hyperglycemia causes the release of proinflammatory cytokines, the induction of reactive radicals, alterations in cardiovascular substrate metabolism, and propagation of coagulation and apoptosis. These all have harmful effects during and after acute myocardial infarction. Recommendations are for strict glycemic control in hyperglycemic patients with acute myocardial infarction, although the target glucose level is still a subject of debate.