The triptan era has been a time of remarkable progress for migraine diagnosis and treatment. In this paper, we review some of the advances achieved in migraine science during this era focusing on 3 themes: lessons from clinical practice, lessons from epidemiology and lessons from pathophysiology. Science has shown that migraine is a disorder of the brain, and that the key events happen in the the trigeminal neuronal pathways, not on blood vessels. Clinical science has led to the observation that migraine sometimes progresses or remits. This in turn led to longitudinal epidemiologic studies focusing on factors that determine migraine prognosis. In addition, these studies raised questions about the mechanisms of migraine progression, including the role of allodynia, obesity, inflammation, and medications as determinants of progression. This in turn opens a new set of scientific questions about the neurobiologic determinants of migraine, as well as of its clinical course, and exciting opportunities to develop new therapies for this highly disabling brain disorder.