The small peptide urocortin (Ucn) has the ability to protect the heart by reducing cardiac cell loss during myocardial ischemia/reperfusion, and improving post-ischemic cardiac performance. Although its mechanism of action is not clearly defined, investigations have revealed that Ucn acts through several kinase pathways, and modulates a group of genes which synergistically minimize mitochondrial damage. Besides cardioprotection, most recent findings suggest a role for Ucn as a cardiac biomarker. Serum Ucn levels may be clinically useful to diagnose cases of mild sub-lethal ischemia, lacking elevation of cardiac enzymes and electrocardiogram changes. Infusion of Ucn may also help reduce the extent of the iatrogenic ischemic/reperfusion injury, associated with cardioplegic arrest.