Cluster headache is a debilitating neuronal headache with secondary vascular changes and is often accompanied by other characteristic signs and symptoms, such as unilateral rhinorrhea, lacrimation, and conjunctival injection. It primarily affects men, and in many cases, patients have distinguishing facial, body, and psychologic features. Several factors may precipitate cluster headaches, including histamine, nitroglycerin, alcohol, transition from rapid eye movement (REM) to non-REM sleep, circadian periodicity, environmental alterations, and change in the level of physical, emotional, or mental activity. The pathophysiologic features have not been completely elucidated, but the realms of neurobiology, intracranial hemodynamics, endocrinology, and immunology are included. Therapy is prophylactic or abortive (or both). Treatment, possibly with combination regimens, should be tailored to the needs of the individual patient.