BACKGROUND: Medications administered long term, such as those used for migraine prophylaxis, are often associated with weight change as a side effect. Such effects may compromise general health status, exacerbate coexisting medical conditions, and affect medication adherence. Weight gain should be of particular concern in patients with migraine, as there is evidence that overweight and obese patients with migraine are at risk for an increased frequency and severity of migraine attacks. OBJECTIVE: This article reviews weight-change data from recent clinical studies of migraine-preventive medications in children, adolescents, and adults with migraine. METHODS: A PubMed search was conducted for English-language articles published between January 1970 and November 2007. Among the search terms were migraine prevention, migraine prophylaxis, migraine treatment, antidepressant drug, beta-adrenergic-receptor blockers, antiepileptic drug, anticonvulsant drug, weight gain, and weight loss. Studies that reported weight-change data (gain, loss, or neutral) were included. When available, double-blind, placebo-controlled studies were selected for review. Open-label, retrospective or prospective trials may also have been included. RESULTS: Most of the migraine-preventive medications classified by the United States Headache Consortium as group 1 based on the high level of evidence for their efficacy--for instance, amitriptyline, propranolol, and divalproex sodium-have been associated with varying degrees of weight gain. The exceptions are timolol, which is weight neutral, and topiramate, which is associated with weight loss. Among the drugs that have been associated with weight gain, a higher incidence of weight gain was observed with amitriptyline and divalproex sodium than with propranolol. CONCLUSION: Weight-change effects require careful consideration when selecting migraine-preventive medications, and weight should be monitored carefully over the course of any migraine treatment plan.