Dihydroergotamine mesylate (DHE) has been used as an acute migraine treatment since 1945, although tolerability with intravenous administration has limited its use. MAP0004 is a novel, orally inhaled, aerosol formulation of DHE that provides pulmonary drug delivery using a pressurized, metered dose inhaler for rapid absorption through lung alveoli. MAP0004 was developed to provide the anti-migraine efficacy of DHE, with fewer systemic effects than intravenous dosing. This review discusses available literature describing the pharmacokinetics, tolerability and efficacy of MAP0004, including data from Phase II and Phase III clinical trials. MAP0004 aerosol DHE provides desirable activation of 5-HT1B/D receptors, resulting in effective anti-migraine effects. Unlike intravenous DHE, MAP0004 is less likely to bind with other serotonergic, adrenergic and dopaminergic receptors, resulting in fewer unwanted side effects. In addition, MAP0004 is less arterioconstrictive than intravenous DHE. Both Phase II and III clinical trials support anti-migraine efficacy with superior tolerability with MAP0004 compared with intravenous DHE. Inhaled rather than intravenous administration should also improve patient acceptance. These data support the future use of MAP0004 as a first-line acute migraine treatment.