Objective.-To show that the intrinsic relationship between sleep and primary headache disorders is based on shared anatomical and physiologic underpinnings. Background.-Sleep-related headaches have been perceived as either the result or cause of disrupted sleep. Design or Methods.-An examination of studies of sleep-related headache disorders that occur during sleep or upon awakening and an explication of principles of anatomy and physiology show the interrelationship of sleep and headache. Results.-Physical conditions (eg, obstructive sleep apnea, depression) that may disrupt sleep and lead to nocturnal or morning headache can often be identified on clinical evaluation or through polysomnography. In contrast, primary headache disorders that can disrupt sleep, such as migraine, cluster headache, chronic paroxysmal hemicrania, and hypnic headache, can readily be diagnosed through clinical evaluation and managed with appropriate medication. Conclusions.-Identifying and classifying the specific type of headache disorder in patients with both headache and sleep disturbance can facilitate a better understanding of the interplay of sleep and headache and can lead to more focused treatment. Patients with poorly defined headaches which occur during sleep or upon awakening, should undergo overnight polysomnography to exclude a treatable sleep disturbance, especially if there in the absence of an underlying psychological disorder or substance/analgesic overuse syndrome.