Ischemic preconditioning offers powerful protection from ischemic necrosis in a wide range of animal species, but does it occur in humans? Support for preconditioning in humans comes from several sources: studies showing increased tolerance to repetitive balloon inflations during angioplasty, some (but not all) studies suggesting that preinfarction angina confers an early beneficial effect, studies showing that patients can develop sudden tolerance to repetitive exercise- or pacing-induced ischemia, cardiothoracic studies of intermittent aortic cross-clamping showing better preservation of myocardial adenosine triphosphate and in vitro studies of isolated human trabecular muscle and isolated human ventricular myocytes that demonstrate a biology consistent with preconditioning. In the future, preconditioning or "preconditioning mimetic" agents have the potential to be applied to a wide array of cardiovascular disorders and might result in better preservation of the heart in instances of cardiopulmonary bypass, heart transplantation, angina and myocardial infarction.