An understanding of the basic anatomy and physiology of the cranial circulation facilitates the assessment and management of patients with headache, particularly vascular-type headaches, such as migraine. At the very least, all pain is perceived and processed in the brain. With migraine it is likely that the fundamental problem and its clinical expression are driven by the CNS; thus study of the brain regarding headache is warranted. As therapy evolves during the 1900s, such an understanding will be necessary, as new and highly specific receptor-targeted compounds allow treatment and improvement of headache in many patients. Since writing this article, the nomenclature for serotonin (5HT) receptors has changed so that any reference herein to 5HTID alpha is now 5HTID and 5HTID beta is now 5HTI beta. This change in nomenclature is discussed in Martig PR, Hoyer D, Humphrey PPA, et al: Alignment of receptor nomenclature with the human genome: Classification of 5HT-1 beta and 5HT-1D receptor subtypes. Trends in the Pharmacological Sciences 17:103, 1996.