The debilitating effect of migraine has fueled the search for more specific agents to treat its characteristic and associated symptoms. Second-generation oral triptans have shown an improved efficacy profile in comparison with the pioneer sumatriptan and with the over-the-counter medications and prescription analgesics that have been staples of migraine treatment. Although all triptans exert effects through the 5-hydroxytryptamine 1B/1D receptors, each triptan has distinctive pharmacokinetic properties that determine its efficacy and tolerability profile. Empirical findings based on clinical trials have led to associations between triptan pharmacology and efficacy. With the expanded treatment choices, the onus is on healthcare providers (especially primary care physicians, who see the majority of patients with migraine) to determine which treatment has an efficacy profile that best suits the individual patient's needs. Patients prefer pharmacotherapy with a rapid onset of action that facilitates complete pain relief and no recurrence. Data from published comparator trials, based on commonly used efficacy end points and pharmacokinetic properties underlying patient-preferred outcomes, are reviewed in this article.