In conclusion, existing data in animals and in man give us no reason to doubt that ischemic preconditioning can and will occur in patients. The clinical implication of endogenous protection will be difficult to determine because of large variability in the preceding pathological conditions and our inability to determine infarct size and its major determinants accurately in man. In addition, myocardium may not only be preconditioned by ischemia but may also become resistant. However, the existing evidence suggests that some pharmacological agents not only lower the threshold for ischemic preconditioning, but are still effective when myocardium has become resistant to ischemic preconditioning. These agents could be useful in patients at risk of infarction provided that the myocardium does not become resistant to continued use of these agents.