Migraine is a highly prevalent, severe, and disabling neurological condition 
with a significant unmet need for effective acute therapies. Patients (~50%) are 
dissatisfied with their currently available therapies. Calcitonin gene-related 
peptide (CGRP) has emerged as a key neuropeptide involved in the pathophysiology 
of migraines. As reviewed in this manuscript, a number of small molecule 
antagonists of the CGRP receptor have been developed for migraine therapy. 
Incredibly, the majority of the clinical trials conducted have proven positive, 
demonstrating the importance of this signalling pathway in migraine. 
Unfortunately, a number of these molecules raised liver toxicity concerns when 
used daily for as little as 7 days resulting in their discontinuation. Despite 
the clear safety concerns, clinical trial data suggests that their intermittent 
use remains a viable and safe alternative, with 2 molecules remaining in 
clinical development (ubrogepant and rimegepant). Further, these proofs of 
principle studies identifying CGRP as a viable clinical target have led to the 
development of several CGRP or CGRP receptor-targeted monoclonal antibodies that 
continue to show good clinical efficacy.