This review highlights the changes in fatty acid homeostasis in the postischemic heart. The impact of restoration of flow (reperfusion) after an ischemic episode on both structural fatty acids (ie, incorporated in phospholipids, the building blocks of cellular membranes) and fatty acids, serving as energy donors by mitochondrial oxidation, are discussed. Attempts to interfere with cardiac fatty acid homeostasis to prevent loss of cardiac function or to restore cardiac performance after reperfusion is also discussed.