Aims: To conduct a systematic review of the literature on the use of botulinum toxin for the treatment of cluster headache. Methods: A systematic review and data quality analysis were performed using PRISMA and GRADE guidelines, respectively. Inclusion and exclusion criteria were outlined prior to the search and aimed to select prospective studies that examined the use of botulinum toxin for the treatment of cluster headache. Results: Three studies resulted from the search that each included 10 to 17 subjects. All three demonstrated significant improvement in the frequency of headaches that occurred as quickly as 1 week following treatment. There was low-quality evidence that botulinum toxin was effective in reducing headache frequency and severity by at least 50%. Injections into the sphenopalatine ganglion may have a higher incidence of adverse events. Conclusion: This review summarizes the only prospectively collected efficacy and safety data regarding the use of botulinum toxin in cluster headache. Off-label use should be considered in certain cases. Further study is warranted to better characterize injection paradigms and patient selection, given the encouraging but limited data available. Keywords: botox, botulinum toxin, cluster headache