Agomelatine, a new antidepressant agent, is a selective agonist of the MT1 and MT2 melatonin receptors. Through this peculiar action this drug, like melatonin, has a key role in synchronizing circadian rhythms, which are known to be perturbed in depressed patients, and to increase neurogenesis and the synthesis of trophic factors. In contrast to melatonin Agomelatine exerts a selective antagonism on the 5HT2c receptors localized on dopamine and noradrenaline nerve terminals in the prefrontal cortex. This mechanism results in an increase of synaptic concentration of both monoamines at the level of a brain area that plays a crucial role in modulating cognitive and emotional function. The synergy between these mechanisms results in synchronizing circadian rhythms and improvement of the decline in the cognitive and affective symptoms often present in severe unipolar depression.