This paper reviews significant work which has been done on ischemic preconditioning since its introduction by Murry et al. in 1986. This is a phenomenon where myocardial cells gain protection against long periods of ischemia by initially being exposed to brief episodes of ischemia followed by reperfusion. The molecular basis of ischemic preconditioning where adenosine, bradykinin and opioids are released, and eventually lead to the opening of mitochondrial ATP-sensitive potassium channels, is discussed in detail. There have been over 33 clinical studies to assess the clinical relevance of ischemic preconditioning. Many of these studies have looked at its benefit in patients undergoing percutaneous transluminal coronary angioplasty; others have looked at its use in open-heart surgery. There is no doubt that many of these studies support the clinical relevance of ischemic preconditioning, however, most of these studies have looked at surrogate markers, such as cardiac enzyme release, and left ventricular ejection fraction, but very few looked at the original endpoint, described by Murry et al., which is cell death. Larger trials, with morbidity and mortality being with the primary endpoints, are needed to confirm the clinical relevance of ischemic preconditioning.