Migraines affect 28 million people in the United States, and most of these individuals experience attack-related morbidity. Six of every 10 patients with migraine treat their headache exclusively with over-the-counter (OTC) products. Overreliance on OTC agents contributes to preventable morbidity and drug-induced headaches. To evaluate the role of OTC drugs in the management of migraine headaches, we performed a qualitative systematic literature search by using MEDLINE (January 1966-April 2002), analyzed the references of articles returned by the MEDLINE search, and reviewed other pertinent literature. In the studied populations, acetaminophen, aspirin, ibuprofen, and an aspirin-acetaminophen-caffeine combination product were shown to be more effective than placebo at reducing moderate or severe migraine pain to mild or no pain by 2 hours after administration. However, published trials of OTC agents have systematically excluded patients enduring morbidity with 50% or more of attacks and/or vomiting with 20% or more of attacks. Patients who experience disability during the predominance of their attacks are poor candidates for OTC-exclusive therapy and should seek a physician's help for migraine-specific prescription drugs. For those with migraine who encounter disability with less than 50% of attacks and/or vomiting with less than 20% of attacks, sole treatment with OTC products is a feasible option. Patients who fail to obtain acceptable relief after an adequate trial of OTC agents also should be referred to a physician. Pharmacists are well positioned to assess whether patients could benefit from OTC agents or should seek a physician's assistance.