Disruption of the sleep-wake cycle is common in primary care, and is intimately interlinked with depression. This presentation aims to review the relationship between circadian rhythms and depression, with an emphasis on the foundation and clinical salience of the relationship. Depression is the most common cause of insomnia, and insomnia is highly prevalent in depression. This association has a well-characterized physiological foundation. Disruption of circadian rhythms and sleep-wake regulation in depression has prognostic and therapeutic implications. Residual sleep-wake disturbance after remission of depression is predictive of relapse, and prominent sleep disturbance predicts a poorer treatment outcome in depression. Disruption of sleep-wake and social rhythms is a bi-directional factor which both increase the vulnerability to depression, while depression has the capacity to further dysregulate social rhythms. Therapeutic strategies that address circadian dysregulation are of value in the adjunctive management of mood disorders. This includes integrating both pharmacological and behavioral strategies; the latter includes sleep hygiene and regulating circadian rhythms.