The prevalence of ice-pick pains and ice-cream headache in migrainous patients and their localisation to the habitual site of migraine headache, suggest that segments of the central pain pathways remain hyperexcitable between spontaneous attacks. Excessive afferent stimulation (flashing lights, noise, strong perfumes) or hypothalamic changes resulting from emotion, stress or the operation of some internal clock may set in motion brainstem mechanisms, including spontaneous unilateral or bilateral discharge of pain pathways. Studies in the experimental animal have shown that certain monoaminergic brainstem nuclei can influence the cerebral circulation unilaterally and that they and the trigeminal system can induce a reflex dilatation of the external carotid circulation. Descending pathways from the same brainstem nuclei cause the adrenal gland to secrete noradrenaline, which in turn can release serotonin from blood platelets. Free serotonin may become adsorbed to the arterial wall, thus increasing sensitivity to pain, augmenting afferent input and adding a pulsating quality to migrainous pain. Both neural and vascular components of migraine implicate monoamines, specifically noradrenaline and serotonin, as neurotransmitters and humoral agents. The recent pharmacological classification of serotonin (5HT) receptors indicates that agonists of a subset of the 5HT1 receptor and antagonists of 5HT2 receptors are most likely to be helpful in the treatment of migraine.