Migraine is a common disabling neurological disorder, associated with headache, nausea, and on occasions vomiting. Zolmitriptan is a widely available serotonin 5HT1B/1D receptor agonist with a long track record in clinical studies and in the treatment of acute migraine. A nasal formulation has been developed that has clear evidence for local absorption, resulting in plasma drug concentrations within 2 minutes of dosing, central nervous system penetration 3 minutes later, and a significant efficacy benefit versus placebo 10 to 15 minutes after dosing. Intranasal zolmitriptan offers advantages to migraineurs, particularly those seeking a more rapid onset of effect without wishing to self-inject, or those with gastrointestinal upset. The comparison of pharmacokinetic and clinical data available from different formulations of zolmitriptan contributes both to the understanding of its mode of action and the characteristics required of an acute migraine treatment if it is to meet patient needs.