Melatonin, the 'hormone of darkness' is a neuronal hormone secreted by the pineal gland and other extra pineal sites. Responsible for the circadian rhythm and seasonal behaviour of vertebrates and mammals, melatonin is responsible for regulating various physiological conditions and the maintenance of sleep, body weight and the neuronal activities of the ocular sites. With its unique amphiphilic structure, melatonin can cross the cellular barriers and elucidate its activities in the subcellular components, including mitochondria. Melatonin is a potential scavenger of oxygen and nitrogen-reactive species and can directly obliterate the ROS and RNS by a receptor-independent mechanism. It can also regulate the pro- and anti-inflammatory cytokines in various pathological conditions and exhibit therapeutic activities against neurodegenerative, psychiatric disorders and cancer. Melatonin is also found to show its effects on major organs, particularly the brain, liver and heart, and also imparts a role in the modulation of the immune system. Thus, melatonin is a multifaceted candidate with immense therapeutic potential and is still considered an effective supplement on various therapies. This is primarily due to rectification of aberrant circadian rhythm by improvement of sleep quality associated with risk development of neurodegenerative, cognitive, cardiovascular and other metabolic disorders, thereby enhancing the quality of life.