The phenomenon of "ischemic preconditioning" has been recognized for almost two decades. In experimental animals and humans, a brief period of ischemia has been shown to protect the heart from more prolonged episodes of ischemia, and reduce the degree of impaired ventricular function or subsequent damage. Ischemic preconditioning is classified into two distinct components: the classic early preconditioning and the delayed or late preconditioning, each with its own biologic mechanism of adaptation. A comprehensive understanding of these mechanisms and application to clinical scenarios has the promise of providing unique opportunities, particularly regarding the development of preconditioning mimetic agents. Administration of these mimetic drugs or procedures could potentially advance the use of preconditioning as a therapeutic tool and/or preventive factor for cardiovascular disease.