(1) A wide array of data regarding acute migraine treatment are available, but few trials strictly adhere to International Headache Society guidelines for patient inclusion criteria.(2) Triptans appear to have similar efficacy profiles, but among newer triptans, almotriptan offers improved tolerability over sumatriptan.(3) Combination indomethacin/caffeine/prochlorperazine most likely has similar therapeutic efficacy to triptan therapy, with further research needed to complete understanding of any potential differences between these treatments.(4) Multi-targeted combination therapy with a triptan plus a non-steroidal anti-inflammatory (NSAID), such as sumatriptan/naproxen sodium, is more effective in acute migraine treatment than monotherapy with either agent alone.(5) It is unclear whether triptans offer clinically relevant benefits over aspirin or NSAIDs in migraine patients. Thus NSAIDs, particularly effervescent aspirin, should be considered the first-line treatment of migraine attacks.