Migraine is a common neurological disorder that is associated with an increase in plasma calcitonin gene-related peptide (CGRP) levels. CGRP, a neuropeptide released from activated trigeminal sensory nerves, dilates intracranial blood vessels and transmits vascular nociception. Therefore, it is propounded that: (i) CGRP may have an important role in migraine pathophysiology, and (ii) inhibition of trigeminal CGRP release or CGRP-induced cranial vasodilatation may abort migraine. In this regard, triptans ameliorate migraine headache primarily by constricting the dilated cranial blood vessels and by inhibiting the trigeminal CGRP release. In order to explore the potential role of CGRP in migraine pathophysiology, the advent of a selective CGRP receptor antagonist was obligatory. The introduction of di-peptide CGRP receptor antagonists, namely BIBN4096BS (1-piperidinecarboxamide, N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl] pentyl] amino]-1-[(3,5-dibromo-4-hydroxyphenyl) methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-, [R-(R*,S*)]-), is a breakthrough in CGRP receptor pharmacology and can be used as a tool to investigate the role of CGRP in migraine headaches. Preclinical investigations in established migraine models that are predictive of antimigraine activity have shown that BIBN4096BS is a potent CGRP receptor antagonist and that it has antimigraine potential. Indeed, a recently published clinical study has reported that BIBN409BS is effective in treating acute migraine attacks without significant side effects. The present review will discuss mainly the potential role of CGRP in the pathophysiology of migraine and the various treatment modalities that are currently available to target this neuropeptide.