Sleep disturbances and disruptions of circadian rhythms are underlying factors in most mood disorders like major depressive disorder (MDD) and bipolar disorder (BD), and their seasonal pattern or seasonal affective disorder (SAD). Decreases in sleep efficiency, total sleep time and sleep quality have all been documented in MDD. In addition to this, depressed patients of all these three categories (MDD, BD, SAD) exhibit profound disturbances in circadian rhythms including the sleep-wake rhythm. Circadian clock dysregulation has been suggested to be due abnormal circadian rhythmicity of gene expression. In particular, CRY1 and CRY2 polymorphisms have been shown to be associated with MDD. Similarly, variations in CRY2, PER2, ARNTL and NPAS2 are associated with SAD. An antidepressant that benefits sleep quality and resynchronize disrupted circadian rhythms will be most useful in treating mood disorders. In this context, the newly introduced melatonergic antidepressant agomelatine with MT1 and MT2 agonistic properties with 5-HT2C antagonism has been documented to be beneficial, as it improves sleep, resynchronizes the disrupted circadian rhythms, and elevates mood. This drug also manifests with fewer adverse effects and is emerging as an effective antidepressant.