Aims: To present a review of the mechanisms of action, available clinical data, and safety profiles of novel migraine therapeutics to inform practice. Methods: PubMed, Medline, and Google Scholar were searched for randomized controlled trials (24 publications), review articles (15 publications), and other pertinent literature (16 publications) discussing the novel migraine therapeutics available between the years 2010 and 2021. All publications were reviewed to assess the mechanism of action, relevant clinical data, and side effect profile for each novel treatment. Therapeutic gain was also recorded in studies that included a placebo arm. Results: A total of 55 studies were included in the final analysis. In the preventive treatment of migraine, novel medications target calcitonin gene-related peptide (CGRP) and fall into either the monoclonal anti-CGRP or gepant class. For the acute treatment of migraine, novel medications fall into either the ditan or gepant class. Several medical devices have been developed for the acute and preventive treatment of migraine. Conclusion: Novel therapeutics are available for both the prevention and acute treatment of migraine headaches. These new medications and neuromodulatory devices appear overall to be safe and effective in the management of migraine headaches.