Physiological aspects of uncoupling of oxidation and phosphorylation are reviewed in the context of involvement of mitochondrial anion carriers. It is assumed that the carriers facilitate electrophoretic translation of fatty acid anion, RCOO-, from the inner to the outer leaflet of the mitochondrial membrane, whereas back movement of the protonated fatty acid, RCOOH, from the outer to the inner leaflet represents flip-flop of RCOOH via the phospholipid bilayer of the membrane. The RCOO- transport seems to be catalyzed by the ATP/ADP and aspartate/ glutamate antiporters, dicarboxylate carrier, and uncoupling proteins (UCP1, UCP2, UCP3L, UCP3s, and plant UCP). The fatty acid uncoupling is shown to be involved in the thermoregulatory heat production in animals and plants exposed to cold, as well as in performance of respiratory functions other than ATP synthesis, i.e., formation of useful substances, decomposition of unwanted substances, and antioxidant defense. Moreover, partial uncoupling might take part in optimization of the rate of ATP synthesis in aerobic cells.