Migraine is a common, often disabling, neurovascular disease that has been shown to be associated with abnormal serotonergic activity. Drugs that modulate serotonin receptors are commonly used in the acute treatment of a migraine attack. Zolmitriptan, a 5-hydroxytryptophan(1B/1D) receptor agonist, is once such drug that is used in acute migraine therapy. Zolmitriptan is FDA approved for the treatment of acute migraine attacks and there is recent literature demonstrating its efficacy in the acute treatment of cluster attacks. It is rapidly absorbed and is detectable in the plasma within 2 - 5 min for the nasal spray formulation and within 15 min for the oral formulations. Zolmitriptan reaches peak plasma levels in 2 - 4 h and significant plasma levels are maintained for up to 6 h and lower levels for over 15 h. As zolmitriptan's metabolism is predominantly hepatic, patients with severe hepatic impairment should not receive zolmitriptan. However, only 25% of zolmitriptan is bound to plasma proteins and thus it is unlikely for drug interactions involving the displacement of highly protein-bound drugs. Zolmitriptan is generally very well tolerated and less than half of patients in clinical trials have reported adverse events, most of which are mild and transient, although rare serious cardiovascular events have been reported with all triptans. When patients are appropriately selected, zolmitriptan is both a safe and effective acute care migraine treatment. In this review the biological role of serotonin and its receptors is covered, followed by an in-depth review of the pharmacodynamics, pharmacokinetics and efficacy of zolmitriptan. Finally, the clinical application of zolmitriptan's use in patients is dicussed.