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Introduction: Migraine is the most common neurological disorder and represents the first cause of disability in under 50s in both genders. Available preventive drugs were primarily developed for indications other than migraine and with an unclear mechanism of action in migraine pathophysiology. Areas covered: This article reviews current preventive treatments and their shortcomings and the road that, through the understanding of calcitonin gene-related peptide (CGRP) role in migraine pathophysiology, carried to the approval of the 3 first-in-class monoclonal antibodies (mAbs) acting on the CGRP pathway. Data from phase 2 and phase 3 clinical trials of erenumab, galcanezumab and fremanezumab, both for episodic and chronic migraine prevention, are consistent for safety and efficacy. Expert opinion: Anti-calcitonin gene-related peptide mAbs have potential advantages over conventional treatments such as ease of use, quick onset of action, persistent efficacy, placebo-like safety profile and absence of pharmacological interactions. Pharmacoeconomic studies should evaluate the economic impact of these drugs taking into account the overall direct and indirect costs related to untreated migraine and to migraine treated with the other available preventive therapies. Given the high cost of these therapies, it is essential to implement all possible strategies to optimize their effectiveness by optimization of patients' selection.