The calcium channel antagonists are a recently developed class of vasodilators that prevent the influx of calcium into vascular smooth muscle. The unique pharmacologic effects of these agents provide a theoretical basis for their use in the treatment of migraine. First, the calcium channel antagonists inhibit the actions of all vasoactive substances on intracerebral smooth muscle via a blockade of the "final common pathway" of cellular contraction. Secondly, the vascular effects of the calcium channel antagonists are selective for intracerebral versus peripheral vessels. Clinically, two specific calcium antagonists (flunarizine, cinnarizine) and two non-specific antagonists (cyproheptadine, amitriptyline) are effective in the treatment of migraine. Further studies will determine whether the calcium channel antagonists, as a class of agents, are effective in the treatment of migraine and other forms of vascular headache. This novel class of vasodilators also provides a powerful tool for the critical evaluation of the vascular theory of migraine.