The neuropeptide calcitonin gene-related peptide is well established as a key 
player in the pathogenesis of migraine. Clinical studies show calcitonin 
gene-related peptide levels correlate with migraine attacks, and decreases in 
this neuropeptide can indicate antimigraine therapy effectiveness. Research has 
revealed a wide distribution of expression sites for calcitonin gene-related 
peptide in the central and peripheral nervous system. Of these, the calcitonin 
gene-related peptide receptor, which binds calcitonin gene-related peptide with 
high affinity, has attracted growing interest as a viable target for 
antimigraine therapies. An incentive to pursue such research is the continuing 
unmet medical need of patients. Triptans have offered some clinical benefit, but 
many patients do not respond and these drugs have important safety 
considerations. Initial calcitonin gene-related peptide-focused research led to 
development of the "gepant" small-molecule calcitonin gene-related peptide 
receptor blockers. Positive efficacy reports concerning the gepants have been 
tempered by safety findings which led to the discontinuation of some of these 
agents. Currently, there is considerable excitement regarding monoclonal 
antibodies against calcitonin gene-related peptide (eptinezumab, galcanezumab, 
fremanezumab) and the calcitonin gene-related peptide receptor (erenumab). To 
date, these monoclonal antibodies have shown promising efficacy in clinical 
trials, with no major safety concerns. If ongoing long-term studies show that 
their efficacy can be maintained, this may herald a new era for effective 
antimigraine therapies.