The etiology of migraine, a neurological disorder, has still not been clearly established, although it may be categorized as a headache disorder with specific characteristics such as focal neurological symptoms preceding or accompanying the headache. Many researchers have suggested genetic predisposition as one of the underlying causes of migraine. An insight into the various pathophysiological mechanisms such as the role of cortical spreading depression, abnormal brain stem activity, trigeminal nerves, calcitonin gene related peptide, nitric oxide and serotonin receptors in the development of migraine, has been conferred in the present article. The accurate diagnosis of migraine and identification of its type is a prerequisite for appropriate therapy. Ample opportunity still exists for the improvement in the safety, efficacy and tolerance capacity of the currently available antimigraine medications, through the design and development of targeted drug delivery system. In the present review, an attempt has been made to highlight all the underlying pathophysiological mechanisms of migraine, its diagnosis, treatment and therapeutic area to be explored including mitigation of biochemical pathways and gene therapy.