An understanding of the pathophysiology and pharmacology of migraine has been driven by astute clinical observations, elegant experimental medicine studies and importantly by the introduction of highly effective selective anti-migraine agents such as the Triptan 5-HT1B/1D agonists. New investigational migraine therapies such CGRP antagonists target key components of the trigeminal sensory neuroinflammatory response and show promise for the future. Cutting edge molecular profiling studies looking at gene expression during chronic pain are now being used to reveal the cell biology of pain and new potential therapeutic targets. Translational neuroimaging research can link the laboratory and the clinic and is now being used to help understand the neural systems biology of migraine. Research into migraine has generated sophisticated hypotheses that encompass primary CNS dysfunction, trigeminovascular activation, pain perception and activation of associated neural circuits involved in affective functions providing a rich framework within which to design and test future migraine treatment strategies.