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Cluster headache is a disabling neurologic disorder that is characterized by daily, attacks of very severe, strictly unilateral pain occurring over a period of weeks or months. Recently, calcitonin gene-related peptide and its receptor complex have garnered attention as promising targets for treating primary headache disorders: particularly migraine and cluster headache. Calcitonin gene-related peptide is found in the trigeminal sensory innervation of major cerebral vessels thought to carry nociceptive information during a headache. Increased levels of calcitonin gene-related peptide have been seen in the ipsilateral jugular venous outflow during an attack phase, and indeed, calcitonin gene-related peptide itself can trigger an attack if administered to a patient in bout, suggesting its distinct role in the generation of attacks. Various monoclonal antibodies targeting calcitonin gene-related peptide and its receptor are emerging as a new frontier in migraine with potential further therapeutic use in cluster headache. This review summarizes the current therapeutic approaches of cluster headache before sharing the potential future role of calcitonin gene-related peptide and its relevance in cluster headache pathology and as targets for future treatment.