Early reperfusion after an organ ischemia is essential to salvage tissue from eventual death. However, abundant evidence suggests that reperfusion also elicits pathophysiological changes responsible for additional tissue injury after restoration of blood flow. Postconditioning (Postcon) defined as rapid sequential intermittent interruption of blood flow applied during early moments of reperfusion has successfully shown to attenuate organ injury, including the heart, spinal cord, brain, kidney, liver, muscle, lung and intestines in the experimental setting. Clinical trials have also revealed the beneficial effect of Postcon on myocardial infarction in patients undergoing percutaneous coronary intervention or coronary artery bypass graft surgery. Although there are some controversial issues regarding the efficacy of protection with Postcon in different animal models with comorbities, most preclinical studies have shown that Postcon is a potent intervention to reduce organ necrosis and apoptosis. Remote or pharmacological Postcon has emerged as alternatives in amelioration of cardiac reperfusion injury. This article will primarily discuss the existing literature regarding protection of Postcon on the heart, but there is a potential for future research into other organ systems to identify beneficial effects of Postcon on tissue reperfusion injury, particularly in patients undergoing surgical revascularization.