The importance of magnesium in the pathogenesis of migraine headaches is clearly established by a large number of clinical and experimental studies. However, the precise role of various effects of low magnesium levels in the development of migraines remains to be discovered. Magnesium concentration has an effect on serotonin receptors, nitric oxide synthesis and release, NMDA receptors, and a variety of other migraine related receptors and neurotransmitters. The available evidence suggests that up to 50% of patients during an acute migraine attack have lowered levels of ionized magnesium. Infusion of magnesium results in a rapid and sustained relief of an acute migraine in such patients. Two double-blind studies suggest that chronic oral magnesium supplementation may also reduce the frequency of migraine headaches. Because of an excellent safety profile and low cost and despite the lack of definitive studies, we feel that a trial of oral magnesium supplementation can be recommended to a majority of migraine sufferers. Refractory patients can sometimes benefit from intravenous infusions of magnesium sulfate.