This paper reviews the recent discovery of clock genes that provide the mechanism for the regulation of circadian and seasonal rhythms in lower organisms and in humans and relates these clock genes to the circadian abnormalities in depression. (1) A subgroup of depressed patients have documented circadian abnormalities in mood, sleep, temperature and neuroendocrine secretion; (2) It is also suggested that seasonal affective disorder (SAD) patients may show an abnormality in their ability to shift their daily circadian rhythms in response to seasonal light changes; (3) The dramatic improvements in some depressions in response to three treatment modalities which manipulate circadian rhythms suggest that circadian abnormalities reported in patients may constitute a core component of the pathophysiology in depression; (4) Mutations in clock genes have been discovered that accelerate or delay circadian cycles; (5) It is hypothesized that 24-hour rhythm abnormalities in major depression and SAD may be due to altered clock genes.