The pineal gland is a interface between light-dark cycle and shows neuro-endocrine functions. Melatonin is the primary hormone of pineal gland, secreted at night. The night-time melatonin peak regulates the physiological functions at dark. Melatonin has several unique features as it synchronises internal rhythm with daily and seasonal variations, regulates circadian rhythm and sleep-wake cycle. Physiologically melatonin involves in detoxification of free radicals, immune functions, neuro-protection, oncostatic effects, cardiovascular functions, reproduction, and foetal development. The precise functions of melatonin are exhibited by specific receptors. In relation to pathophysiology, impaired melatonin secretion promotes sleep disorder, cancer progression, type-2 diabetes, and neurodegenerative diseases. Several reports have highlighted the therapeutic benefits of melatonin specially related to cancer protection, sleep disorder, psychiatric disorders, and jet lag problems. This review will touch the most of the area of melatonin-oriented health impacts and its therapeutic aspects.