In diurnal species, nocturnal melatonin secretion coincides with the habitual hours of sleep, in contrast to nocturnal animals which are at the peak of their activity while producing melatonin. Studies in humans, diurnal non-human primates, birds and fish show that melatonin treatment can facilitate sleep initiation during the daytime or improve altered overnight sleep. Behaviorally, the sleep-promoting effects of melatonin are distinctly different from those of common hypnotics and are not associated with alterations in sleep architecture. The effects of melatonin on sleep are mediated via specific melatonin receptors and physiologic doses of the hormone, those inducing circulating levels under 200pg/ml, are sufficient to promote sleep in diurnal species. Aging reduces responsiveness to melatonin treatment and this correlates with reduced functional potency of melatonin receptors. Since melatonin receptors are present in different tissues and organs and involved in multiple physiologic functions, using physiologically relevant doses (0.1–0.3 mg, orally) and time of administration (at bedtime) is recommended, in order to avoid known and unknown side effects of melatonin treatment.