Introduction: Disturbances of circadian rhythms and sleep play an important role in various types of mood disorders like major depressive disorder (MDD), bipolar depressive disorder (BPD) and seasonal affective disorder (SAD). Malfunctioning of the SCN-pineal-melatonin link has been suggested as the main cause for these disorders. As a rhythm-regulating factor and as a hormone involved in the regulation of sleep, melatonin is essential for the control of mood and behavior. Areas covered: Melatonin's involvement in various mood disorders is reviewed based on studies undertaken in patients with MDD, BPD and SAD. The chemistry and metabolism of the newly introduced antidepressant, agomelatine, a MT1/MT2 melatonin receptor agonist and 5-HT2c antagonist in brain areas involved in mood regulation are also discussed. Its clinical role in mood regulation, agomelatine's efficacy, safety and tolerability are also reviewed. Expert opinion: Agomelatine, a melatonergic antidepressant with a rapid onset of action, has been shown effective in various types of mood disorders (e. g., MDD, BPD, SAD). Some studies find it superior to other common antidepressants (SSRIs, SNRIs) that are in clinical use today. Agomelatine's efficacy, good tolerability and safety profile suggest that it may become a preferred antidepressant in the near future.