Migraine is one of the most frequent neurological disorders affecting up to 15% of the general population. Many patients require not only management of individual migraine episodes but also prophylactic treatment. beta-adrenoceptor blockers, flunarizine and valproic acid have been established as first-line agents for the prophylaxis of migraine attacks. Among the beta-adrenoceptor blockers propranolol and metoprolol are best documented and hence deserve preferential use. On the other hand, it appears that other beta-adrenoceptor blockers, perhaps with the exception of those with intrinsic sympathomimetic activity, can be equally effective. Uncertainties regarding the relative merits of various treatment modalities are largely caused by lack of adherence to specific requirements for clinical trials on migraine prophylaxis. Therefore, this article reviews internationally recommended conditions for reliable studies on migraine prophylaxis and appraises individual agents in the light of these criteria.