This article reviews the literature for evidence of a disorder of circadian rhythm and hypothalamic function in cluster headache. Cluster headache exhibits diurnal and seasonal rhythmicity. While cluster headache has traditionally been thought of as a vascular headache disorder, its periodicity suggests involvement of the suprachiasmatic nucleus of the hypothalamus, the biological clock. Normal circadian function and seasonal changes occurring in the suprachiasmatic nucleus and pineal gland are correlated to the clinical features and abnormalities of circadian rhythm seen in cluster headache. Abnormalities in the secretion of melatonin and cortisol in patients with cluster headache, neuroimaging of cluster headache attacks, and the use of melatonin as preventative therapy in cluster headache are discussed in this review. While the majority of studies exploring the relationship between circadian rhythms and cluster headache are not new, we have entered a new diagnostic and therapeutic era in primary headache disorders. The time has come to use the evidence for a disorder of circadian rhythm in cluster headache to further development of chronobiotics in the treatment of this disorder.