Migraine is a primary headache disorder characterized by recurrent attacks. Acetaminophen, nonsteroidal anti-inflammatory drugs, triptans, antiemetics, ergot alkaloids, and combination analgesics have evidence supporting their effectiveness in the treatment of migraine. Acetaminophen and nonsteroidal anti-inflammatory drugs are first-line treatments for mild to moderate migraines, whereas triptans are first-line treatments for moderate to severe migraines. Although triptans are effective, they may be expensive. Other medications such as dihydroergotamine and antiemetics are recommended for use as second- or third-line therapy for select patients or for those with refractory migraine. The pharmacologic properties, potential adverse effects, cost, and routes of administration vary widely, allowing therapy to be individualized based on the pattern and severity of attacks. Several treatment principles, including taking medication early in an attack and using a stratified treatment approach, can help ensure that migraine treatment is cost-effective.