Case presentation: SB is a 48-year-old man who suffered an acute anterior myocardial infarction and received fibrinolytic therapy. The patient died 12 hours after reperfusion. KR is a 68-year-old diabetic woman who underwent conventional coronary artery bypass graft surgery and developed low output syndrome after reperfusion postoperatively. VA is a 55-year-old man who developed a stunned myocardium after percutaneous coronary reperfusion. What is reperfusion injury, and why is it important? Reperfusion of coronary flow is necessary to resuscitate the ischemic or hypoxic myocardium. Timely reperfusion facilitates cardiomyocyte salvage and decreases cardiac morbidity and mortality. Reperfusion of an ischemic area may result, however, in paradoxical cardiomyocyte dysfunction, a phenomenon termed “reperfusion injury.” Modalities for reperfusion include not only thrombolysis, but also percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and cardiac transplantation. Reperfusion injury has been observed in each of these situations. We discuss here the fundamental principles of reperfusion injury from a mechanistic and pharmacological standpoint.