Thyroid hormones control growth, development and metabolism in animals. The iodothyronine deiodinases catalyze the removal of an iodine residue from outer or inner ring of the pro-hormone thyroxin (T4) molecule, thus producing either the active form triiodothyronine (T3; activation) or inactive metabolites (reverse T3; inactivation), respectively. Type 1 deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on thyroid metabolism in physiology and pathology. Type 2 deiodinase (D2) initiates thyroid hormone signaling by activating the T4 to the biologically active T3 molecule followed by gene expression on a cell-specific basis. Expression of D2 in such specific tissues as hypothalamus, pitutary, brain, brown adipose tissue, cochlea, retina, skeleton demonstrates the role of enzyme in physiology of these organs suggesting further therapeutic application. The current review intended to provide an updated picture of the recent advances concerning the molecular properties of D1 and D2 as well as their role in physiology.