Migraine headache is a chronic, painful, disabling and potentially progressive, condition primarily occurring in early and middle adulthood. For many patients, daily activities are impaired by the sudden and unpredictable occurrence of migraine attacks. In recent years, significant progress has been made in the field of migraine treatment. For the acute treatment of migraine attacks, 5-hydroxytryptophan(1B/D) agonists (so called triptans), were the most innovative development, successfully aborting attacks in less than 1 h. The search for innovative drugs usable for migraine prevention, however, was less successful, mainly due to the lack of reliable and predictive animal models. Recently, neuromodulators such as valproic acid and topiramate, initially developed as anticonvulsants, have been shown in large clinical trials to be effective in the prevention of migraine. As for the acute treatment of migraine attacks more than 10 years ago, large clinical trial programs are now setting new standards for evidence-based medicine in migraine prevention. This review summarizes the current options in migraine prevention with special emphasis on clinical trial design and new developments such as topiramate.