Disruption of circadian clocks is strongly associated with mood disorders. "Chronotherapies" targeting circadian rhythms have been shown to be very effective treatments of mood disorders, but still are not widely used in clinical practice. The mechanisms by which circadian disruption leads to mood disorders are poorly characterized and therefore may not convince clinicians to apply chronotherapies. Hence, in this review, we describe specific potential mechanisms, in order to make this connection more credible to clinicians. We believe that four major features of disrupted clocks may contribute to the development of mood disorders: 1) loss of synchronization to environmental 24-hour rhythms, 2) internal desynchronization among body clocks, 3) low rhythm amplitude, and 4) changes in sleep architecture. Discussing these attributes and giving plausible examples, we will discuss prospects for relatively simple chronotherapies addressing these features that are easy to implement in clinical practice.