A biological clock exists in the brain of all mammals together with man. The corollary of the pineal indole hormone melatonin on the life span of mice, rats and fruit flies has been deliberate using various approaches. Melatonin is a previous and omnipresent molecule in nature showing numerous mechanisms of action and functions in almost every living organism. Melatonin’s actions in organisms are more extensive than formerly envisaged. Melatonin is produced at night by the pineal gland and signals darkness to the organism to facilitate harmonization of the circadian clock with the ambient day–night cycle. Melatonin production and secretion are synchronized by sunlight sensed by the eyes and control circadian rhythms. In both in vitro and in vivo investigations, melatonin protected healthy cells from radiation- induced and chemotherapeutic drug–induced toxicity. The aim of this review is to explain the role of melatonin in various disease conditions.