The main role of insulin in the heart under physiological conditions is obviously the regulation of substrate utilization. Indeed, insulin promotes glucose uptake and its utilization via glycolysis. Insulin, promoting glucose as the main cardiac energy substrate, reduces myocardial O(2) consumption and increases cardiac efficiency. Moreover, insulin seems to augment cardiomyocyte contraction, while it affects favorably myocardial relaxation, increases ribosomal biogenesis and protein synthesis, stimulates vascular endothelial growth factor (VEGF) and thereby angiogenesis, suppresses apoptosis, promotes cell survival and finally ameliorates both myocardial microcirculation and coronary artery resistance, leading to increased blood perfusion of myocardium. Thus, insulin acts directly on heart muscle, and this action is mediated principally through PKB/Akt signal pathway. Under pathological conditions, such as type 2 diabetes, myocardial ischaemia, and cardiac hypertrophy, insulin signal transduction pathways and action are clearly modified. In this review we summarize the evidence that the heart is an important target of insulin action and that elimination of these actions is important in disease states.