The review focuses on the neuroprotective mechanisms of therapeutic hypothermia from the standpoint of metabolic depression and genomic reprogramming of neurons that develop when brain temperature decreases. The concept of hypothermic pre-conditioning based on the development of typical nonspecific reactions for the formation of the cytoprotective phenotype of neurons due to potentially dangerous stimuli, such as ischemia, reperfusion, and hypothermia, was used to explain the effects of low temperatures. The data confirming the role of therapeutic cerebral hypothermia as a technique of selective brain exposure to mild cold for the neuroprotection and correction of temperature balance disorders are shown. The approach to therapeutic hypothermia as a hypothermic pre-conditioning allows to significantly expand the scope of its use in various procedural variants. © 2019, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.