Calcitonin Gene-Related Peptide (CGRP) receptor antagonists and triptans are the lime-lighted targets for migraine treatment for the past two decades. However the hypothetical theories of migraine occurrence (including the reason behind initiation) as well as the complex nature of protein and unclear mechanism of the small molecule drug interaction on the receptors, still exists till date making it a challenging task for scientists to move forward in migraine research. Several pharmaceutical companies and research laboratories worked on anti-migraine drugs and even found out some efficacious, selective and potent drugs in the recent years but failed in the later stages of clinical trials due to different reasons. Hence during the course of this article we shall cover the recent advances, breakthroughs and perspectives in migraine therapy.