Slightly over 30 years ago the pineal gland was considered physiologically inconsequential. Even after the discovery of melatonin in the late 1950s (Lerner et al., 1959) and the demonstrations that the metabolic (Axelrod et al., 1965) and endocrine (Hoffman and Reiter, 1965) activities of the gland were influenced by the prevailing light: dark environment, scientists and clinicians were slow to accept the idea of a functional role for the gland and for melatonin in humans. In the intervening years, however, an overwhelming amount of data has been amassed illustrating the remarkable and far-ranging effects of the pineal gland and its hormone melatonin. While there are certain subdisciplines of medicine where the pineal gland is not yet given serious consideration as being functionally relevant, others, i.e., endocrinology, psychiatry, reproductive medicine, and neurological sciences, acknowledge the importance of this multifaceted gland in clinical medicine. It is very likely that further research will reveal the unequivocal importance of melatonin in human physiology and pathophysiology. Considering melatonin acts in every cell, there is very likely not a system that escapes the influence of this important hormone and metabolic regulator.