The feasibility of myocardial reperfusion induced by coronary thrombolysis stimulated marked changes in the management of patients with acute myocardial infarction. Despite the demonstrable successful recanalization achieved in many patients, effective tissue reperfusion has not necessarily been achieved. Furthermore, factors defining the risk/benefit relationships of reperfusion, the extent to which salutary effects on jeopardized myocardium can be anticipated, and the ultimate long-term benefit conferred on the patient all require further definition. Widespread implementation of interventions utilized to induce myocardial reperfusion should be based on thorough characterization of the functional and metabolic responses of the heart to reperfusion. This selective review considers reperfusion within the context of an extensive body of information pertinent to the pathophysiological mechanisms underlying ischemic injury and discusses the potential favorable and unfavorable responses to reperfusion.