Melatonin is synthesized and secreted during the dark period of the light-dark cycle. Thus, melatonin has an obvious association with sleep, at least in diurnal animals. Rhythmic nocturnal melatonin secretion is directly generated by the circadian clock, located in mammals within the suprachiasmatic nuclei (SCN), and is entrained to a 24-h period by the light-dark cycle. The periodic secretion of melatonin may be used as a circadian mediator to any system than can “read” the message. In addition, direct effects of the hormone on the SCN could explain some of melatonin effects on the circadian system. Duration of melatonin nocturnal secretion is directly proportional to the length of the night and it has been demonstrated experimentally to be the critical parameter for photoperiod integration. The two main hypotheses to explain the action of melatonin are the duration hypothesis (supporting that night length is coded by the duration of the melatonin secretory phase) and the coincidence hypothesis (holding that physiological responses are linked to the existence of a diurnal rhythm in sensitivity to melatonin). The sites and mechanisms of action of melatonin for circadian and photoperiodic responses are far from being elucidated, but action through specific membrane receptor sites is well documented. In view of melatonin s lipophilic nature, interactions with specific intracellular proteins like calmodulin or tubulin, or with nuclear receptor sites, have also been considered, whereas the physiological significance of the documented antioxidant effect of melatonin remains to be settled. Melatonin seems to act as an “arm” of the circadian clock, giving a time-related signal to a number of body functions; one of these, the circadian organization of an organism's defence, is discussed in some detail as an example.