The authors of this review generalize and analyze the published data, as well as their own findings, related to melatonin-mediated interaction of the pineal gland (the brain epiphysis) with the hypothalamo-hypophysealthyroid axis (HHTA). The review deals with (i) historical aspect of development of the concepts on neuroendocrine mechanisms underlying the control of functions of the thyroid gland, (ii) data on circadian and seasonal rhythms of the functioning of the epiphysis and HHTA, (iii) basic facts about direct and feedback connections between the brain epiphysis and HHTA, and (iv) overview of the experimental data on age-related changes in the epiphysis-thyroid axis.