Objective: Disturbances in circadian rhythms have been associated with major depression and may be an underlying mechanism for the disorder. Resynchronisation of circadian rhythms may provide a new approach to treatment, especially by manipulating melatonin secretion. Melatonin is secreted at night and is a stable marker of circadian rhythms. The timing of its secretion can be changed by exogenous melatonin, agonism of specific melatonin receptors in the suprachiasmatic nucleus, its suppression by light and by sleep deprivation. Method: As part of a series of papers ['Chronobiology of mood disorders' Malhi & Kuiper. Acta Psychiatr Scand 2013; 128 (Suppl. 444): 2-15; and 'Getting depression clinical practice guidelines right: time for change?' Kuiper et al. Acta Psychiatr Scand 2013; 128 (Suppl. 444): 24-30.] addressing chronobiology, in this article, we conducted a selective review of studies that have examined the antidepressant effects of exogenous melatonin, light therapy, sleep deprivation and melatonin receptor agonists. Results: Antidepressant effects were identified for bright light therapy, especially for seasonal affective disorder; sleep deprivation, although its antidepressant effect is time limited; and for the novel antidepressant agomelatine with agonistic properties for the MT1 and MT2 receptors and antagonism of 5HT(2c) receptor. The role of melatonin as an antidepressant has yet to be demonstrated. Conclusion: Shifting the circadian secretion of melatonin using the strategies reviewed offers a new approach to treating depression.