One of the main endogenous mechanisms of protection in reducing cellular energy resources is the system of ATPsensitive potassium (KATP) channels, which is considered a central metabolic cell sensor for its energy supply. These channels have neuro-, cerebro-, cardio-, nephroprotective effects, which are based on inhibition of excitability and metabolism, reduction of β-amyloid toxicity and normalization of bioenergetic processes with the preservation of high content of ATP. Their opening may have an analgesic effect, which is mediated by the release of endorphins, enkephalins and activation of opioid receptors, and may prevent morphine withdrawal syndrome. Also, the opening of these channels can be used to prevent hormonal disorders, elimination of bronchospasms and hyperactivity of the urinary system, and erectile dysfunction of neurogenic and vascular etiology, to improve hair growth and to normalize the work of skeletal muscles at hypokalemic paralysis. However, they have a special role in the cardiovascular system, because they implement the relationship between the energy resource of the heart, its electrical and contractile functions. At the base of their cardioprotective action are the inhibitory processes that occur due to changes in cardiohemodynamic and metabolism. In particular, moderate lowering of blood pressure, prevention of reperfusion increase of general-peripheral resistance and resistance of coronary vessels, and relative preservation of indicators of myocardial contractility during reperfusion. Also, the preventing a significant increase of excess NO by inducible (by iNOS) and by salvage (by NADH-dependent nitrate reductase) NO synthesis and, conversely, increasing the protective constitutive NO synthesis and the sphingosine content. Important for cardioprotection is significant inhibition of the formation of active forms of oxygen and nitrogen, and the preservation of a high activity of antioxidant enzymes, reduction of the formation of pathogenic in the conditions of myocardial ischemia LTC4 and ТхB2, inhibition of ATP degradation, stimulating of the heme oxygenase reaction, membrane protection and preventing opening of the mitochondrial permeability transition pore, and inhibition of apoptosis and necrosis of cardiomyocytes.