Ischemic preconditioning is among the most consistent and powerful modes of reducing myocardial infarct size. Although several clinical studies have suggested that the human heart can be preconditioned, controversy exists in both the experimental and clinical literature as to whether the senescent heart can be preconditioned. The authors recently reported that older patients (> or = 60 years of age) in the Thrombolysis in Myocardial Infarction-4 study appeared to benefit from a history of angina prior to acute myocardial infarction. This observation may lead to a clinical counterpart to successful preconditioning in the older heart.