Experimental data indicate that moderate uncoupling oxidative phosphorylation induces reduction in production of reactive oxygen species (ROS) and promotes an increase in survival of neurons and cardiomyocytes under hypoxia and re-oxygenation conditions. Uncoupling proteins (UCP) are expressed by cardiomyocytes and neurons. These proteins are involved in the thermogenesis, inhibit ROS generation by mitochondria, reduce deltaphi, elevate respiration rate of these organelles. It was established that UCP contributed to the elevation of cardiomyocyte and neuron tolerance of an impact of hypoxia and re-oxygenation. They also promote cell resistance to oxidative stress. Experimental data indicate the important role of the UCP in the neuroprotective and cardioprotective effects of ischemic preconditioning. At the same time, real contribution of the UCP in preconditioning is still to be verified.