Melatonin (N-acetyl-5-methoxytryptamine) is a molecule known to be produced in multiple cells and organs. It acts at the level of the biological clock, the suprachiasmatic nuclei, to modulate their activity, thereby influencing circadian rhythms, and also sleep processes. The clinical application of melatonin in the treatment of human mental disorders is still in its infancy. Until now, melatonin only has been used in psychiatry because of its hypnotic, resynchronizing and antioxidant actions. In this review, we hypothesized that melatonin might play an important role as an adjuvant therapy, in mental disturbances, due to other properties including its anti-inflammatory, antinociceptive, anxiolytic, drug detoxification properties, protective actions against osteoporosis, etc. Complex interactions occur between the brain and the immune system and currently is accepted that psychological and psychiatric illness can compromise immune and hormonal functions. Altered psychological states often influence the susceptibility of an individual to illness or modify the course of the illness and its prognosis. The present review discusses on the advantages of the co-treatment with melatonin and recent patents in three major psychiatric disorders: depression, bipolar syndrome and schizophrenia. The findings suggest new vistas in both the pathophysiology and the pharmacology of mental disorders.