Circadian rhythms pervade all aspects of our physiology, from sleep/wake cycles, body temperature, hormone levels, and even cognition, attention and mood. It has long been recognised that mood disorders are associated with altered circadian function, with sufferers of depression often displaying blunted or abnormal rhythms of temperature, cortisol, noradrenaline, thyroid stimulating hormone, blood pressure and melatonin. We have found that animal models of depression also display disrupted behavioural, hormonal and gene expression rhythms. Current therapies do not address these symptoms. The atypical antidepressant agomelatine, which is an agonist at melatonin receptors (MT1 and MT2) and an antagonist at the 5-HT2C receptor, can phase advance and synchronise circadian rhythms when administered at the appropriate time of day. Furthermore, clinical trials have demonstrated agomelatine treatment significantly reduces HAM-D scores and increases the rate of response compared to placebo for sufferers of major depressive disorder. In this presentation, we review the relationships between circadian rhythms and depression, and discuss recent studies on potential targets of agomelatine.