Summary: Migraine headache can be a debilitating condition that confers a substantial burden to the affected individual and to society. Despite significant advancements in the medical management of this challenging disorder, clinical data have revealed a proportion of patients who do not adequately respond to pharmacologic intervention and remain symptomatic. Recent insights into the pathogenesis of migraine headache argue against a central vasogenic cause and substantiate a peripheral mechanism involving compressed craniofacial nerves that contribute to the generation of migraine headache. Botulinum toxin injection is a relatively new treatment approach with demonstrated efficacy and supports a peripheral mechanism. Patients who fail optimal medical management and experience amelioration of headache pain after injection at specific anatomical locations can be considered for subsequent surgery to decompress the entrapped peripheral nerves. Migraine surgery is an exciting prospect for appropriately selected patients suffering from migraine headache and will continue to be a burgeoning field that is replete with investigative opportunities.