Postconditioning, a series of mechanical interruptions of reperfusion after ischemia, prevents ischemia/reperfusion injury in myocardial infarction. The extensive studies of postconditioning in myocardial infarction have led to clinical trials. This article reviews the protective effects of postconditioning against ischemia from the heart to the brain and provides insights on how studies of postconditioning in the field of heart ischemia have shed light on postconditioning of the brain. Because brain ischemia has many mechanisms in common with heart ischemia, it is logical to test whether postconditioning protects against brain ischemia as well. A few groups have reported that postconditioning reduces infarct size in focal cerebral ischemia and improves deficits of short-term memory and motor coordination after global cerebral ischemia. However, many outstanding issues remain elusive regarding the protective effects of postconditioning against cerebral ischemia. Future studies should further identify parameters that generate the strongest protection for postconditioning against cerebral ischemia and should study whether postconditioning provides long-term protection. In addition, clarification of the underlying protective mechanisms should be pursued. This will certainly enhance our understanding of this novel phenomenon and may provide important clues for developing pharmacological analogues for stroke treatment.