Migraine is a complex neurological disorder that in recent years has received more and more attention. Knowledge regarding this primary headache has increased substantially, both with respect to its pathogenesis and how to effectively treat its symptoms. Over the years, the proposed location of the onset of migraine has moved from the periphery of the nervous system toward deeper parts of the brain. Migraine can be viewed as an inherited failure of trigeminal sensory processing with abnormal neuronal excitability in the trigeminal nucleus caudalis, which, in turn, causes central sensitization and amplification of the pain. Increased activation of the trigeminal nerve during a migraine attack causes release of the calcitonin gene-related peptide (CGRP) inside and outside the BBB. Within the CNS, CGRP promotes trigeminal sensory input and facilitates central sensitization. The future introduction of CGRP antagonists in clinical practice could represent significant progress for acute migraine therapy.