Migraine affects approximately 18% of women and 6% of men, and has an immense impact on quality of life and productivity. Advancement in therapeutic options has been slow. For many patients with difficult-to-treat migraine, the appropriate use of dihydroergotamine mesylate (DHE) can result in treatment success and unprecedented patient satisfaction. Migraine treatment guidelines regarding the role of DHE are highlighted. An overview of the market for antimigraine drugs is provided in the context of DHE, since its introduction in 1943, and the novel agents that are likely to be available in the near future. An extensive literature search was undertaken using Medline and the Cochrane Systematic Review and Clinical Trial databases. An understanding of which migraine patients are likely to benefit maximally from treatment with DHE in its various forms. In the most difficult patient groups - including those with status migrainosus, migraine recurrence, medication-overuse headache, and chronic daily headache - DHE has therapeutic efficacy superior to other agents. The side-effect profile of DHE is more benign than is often perceived and should not be a deterrent for use in well-chosen cases.