Agomelatine is a novel agent that is under late-stage development as a potential antidepressant. Compared with available antidepressant agents, the drug may have a distinct mechanism of action, with significant interactions with melatonin receptors, in addition to serotonergic brain systems. Agomelatine has been shown to be active in preclinical models indicative of antidepressant activity and the results of a large-scale clinical trial programme, conducted in major depressive disorder, indicate both antidepressant activity and a favourable tolerability profile. As agomelatine may have a pharmacological profile and mechanism of action distinct from available agents, it may come to represent a valuable additional treatment option in those patients who do not respond fully or who prove unable to tolerate the side effects of existing antidepressants.