Migraine is a common primary headache disorder often associated with significant disability. While many individuals are able to limit therapy to acute treatment of attacks, others need medication to reduce the attack frequency and/or severity. Evidence-based guidelines exist regarding indications and goals for migraine preventive treatment. The specific prophylactic approach needs to be individualized taking into account multiple variables. Medications used in this task vary widely in proven efficacy and presumed mechanisms of action. This review's goal is to discuss the issues that guide the decision-making process in migraine preventive treatment.