Mitochondria (Mt) play a key role in the physiology and pathology of humans and animals. Signaling from Mt has divergent physiological and pathophysiological consequences. Critical lack of oxygen causes Mt dysfunction, while adaptation to intermittent hypoxia training (IHT) leads to positive changes in Mt. The focus of this review is to summarize the current knowledge about the mechanisms of IHT impact on Mt structure and functions in compare with the effects of acute hypoxia (AH). It was shown that AH causes mitochondrial swelling, vacuolization of organelles, disorganization and destruction of Mt membranes. When exposed to IHT, the increase in the total number of Mt, the reduction of the number of structurally modified organelles, the appearance of energetically active Mt with vesicular cristae, the microMt formation are observed. AH is associated with oxidative damage, calcium dyshomeostasis, defective ATP synthesis, or induction of the permeability transition pore. Under IHT, the low level of ROS production is protective and serves as a trigger for adaptive responses. IHT leads to reprogramming of Mt metabolism, providing adequate ATP production. Activation of potassium transport in the Mt matrix during IHT is a protective mechanism against Ca2+ overload caused by AH. Mt energy production in brainstem neurons is directly related to the regulation of neurotransmitters - glutamate and GABA which involved in the respiratory rhythmogenesis formation. All adaptive reactions to hypoxia are regulated by HIF-factors (HIF-1, HIF-2, HIF-3). Each of HIF-subunits plays a certain role depending on the mode of hypoxic stress. These peculiarities can be important when choosing a mode of IHT for the prevention and treatment of various diseases. New data about the HIF organ specificity provide potential pharmacological regulation of HIFs as a new therapeutic tool.