Cortical spreading depression is probably the event underlying the aura of migraine, and biochemical and other studies suggest that a state of increased excitability of central neurons may lead to development and propagation of cortical spreading depression. Anatomical studies delineate some of the sites involved in the central processing of craniovascular nociception. 5-Hydroxytryptamine receptors, particularly 5-HT1, exist at both neural and vascular sites and are implicated in the pathogenesis of migraine. Studies in tension-type headache suggest that its pathogenesis is multifactorial, with contributions from both central and peripheral factors.