Migraine headache affects about 12% of Western populations and is the third most common disease worldwide (sixth in terms of disability). In 1993, triptans were introduced in the United States as a new treatment for managing migraine attacks, but their use is limited by lack of response and safety concerns in some patients. Treatment options for patients with migraine who fail or cannot tolerate triptans include switching to another medication or adding an adjunctive medication. Desirable characteristics reported by patients for acute treatment of migraine attacks include complete pain relief, fast onset of action, and no pain recurrence. Diclofenac is a nonsteroidal anti-inflammatory medication that has been established as effective for acute treatment of migraine by the American Headache Society based on available evidence. Diclofenac potassium for oral solution is rapidly absorbed, achieving maximal plasma concentrations in 15 min, which coincides with a rapid onset of effect. In a comparison of diclofenac potassium for oral solution with diclofenac potassium tablets, the solution achieved a significant reduction in headache intensity beginning at 15 min compared with 60 min for the tablet. Across randomized clinical trials, approximately 25% of patients were pain free 2 h after administration of diclofenac oral solution and the effects were maintained over a 24-h period. Diclofenac potassium for oral solution is well tolerated; the most common adverse events are dizziness and gastrointestinal complaints, with incidences similar to placebo. No serious adverse events have been reported in clinical trials of diclofenac potassium for oral solution in the acute treatment of migraine. Diclofenac oral solution may offer rapid and sustained pain relief for patients who do not achieve pain resolution with other medications. In addition, patients who experience central sensitization with allodynia may benefit from the cyclooxygenase-blocking activity of diclofenac, which is needed in this advanced phase of migraine.