Melatonin has a diverse range of physiological effects in humans. Reported effects include modulation of the sleep-wake, thermoregulatory, cognitive, cardiovascular and immune systems. While integrating these broad-ranging effects is difficult when current paradigms are used, the diverse effects of melatonin on human physiology may be better understood by shifting our theoretical perspective. Traditionally, research has treated melatonin as a classical hormone for which a defined effect in physiological systems and a mechanism of action can be elucidated. In this article, we suggest that it may be more appropriate to view melatonin as an evolutionally stable timing signal to which each species has adapted the timing of physiological processes. From this perspective, it appears that the physiological role of melatonin in humans falls into two categories. The first relates to the self-regulation of circadian timing by the suprachiasmatic nucleus-pineal complex. The second relates to the promotion of restorative or anabolic physiological processes. In humans, elevated melatonin levels have been associated with reduced core temperature, increased heat loss, decreased cardiovascular output, reduced alertness and enhanced immune responsiveness. Taken together, these changes suggest that melatonin may increase the propensity for physiological processes promoting nocturnal sleep or processes that occur during the sleep period.