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Lanfranco Pellesi,1 Roberto De Icco,2,3 Mohammad Al-Mahdi Al-Karagholi,1 Messoud Ashina1,4 1Danish Headache Center, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 2Headache Science Center, IRCCS Mondino Foundation, Pavia, Italy; 3Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; 4Danish Headache Knowledge Center, Rigshospitalet Glostrup, Glostrup, DenmarkCorrespondence: Lanfranco PellesiDanish Headache Center, Faculty of Health and Medical Sciences, University of Copenhagen, Vagtelvej 61, Copenhagen 2000, DenmarkTel +393409383056Email lanfranco.pellesi@gmail.comAbstract: The involvement of calcitonin gene-related peptide in migraine and cluster headache has led to the recent development of new therapies. Galcanezumab, a novel monoclonal antibody targeting the calcitonin gene-related peptide, is approved for the migraine prevention and has recently been tested for the prevention of cluster headache. Two clinical trials have been conducted to investigate the efficacy and safety of galcanezumab in episodic cluster headache and chronic cluster headache. While efficacy endpoints were not met in the chronic subtype, galcanezumab reduced the weekly frequency of attacks in patients with episodic cluster headaches. In both studies, the antibody was well tolerated. This review summarizes and critically reviews the available data regarding the rationale behind targeting the calcitonin gene-related peptide with galcanezumab for the prevention of cluster headache.Keywords: cluster headache, calcitonin gene-related peptide, CGRP, antibody, LY2951742