The maximum absolute response rate with oral triptans, as measured in clinical trials by the incidence of relief from migraine pain at 2 hours after taking medication, is approximately 70%. Therefore around 30% of patients fail to respond to a particular triptan. Nonresponse is likely to be due to a variety of factors, including low and inconsistent absorption, use of the medication late in an attack, inadequate dosing, and variability in individual response. Evidence from recent clinical trials, however, confirms the common clinical observation that patients with a poor response to one triptan can benefit from subsequent treatment with a different triptan. Two-hour pain-relief rates of 25% to 81% using alternative triptans (naratriptan, almotriptan, eletriptan, zolmitriptan, and rizatriptan) have been reported in patients who were described as poor responders to sumatriptan. Physicians should remain vigilant in assessing the response to acute therapy and take advantage of simple clinical questionnaires that have been developed to facilitate the recognition of those patients who require and may benefit from a change in acute therapy.