Stroke is among the leading causes of death and serious disability in the United States. Treatment of the acute ischemic stroke patient requires a multidisciplinary approach involving first-responders, emergency department personnel, neurologists, advanced imaging experts and endovascular specialists with neurosurgical support. Contemporary stroke treatment is a rapidly advancing field. New developments in pharmacologic and endovascular stroke therapy require thoughtful trial design and expeditious trial implementation to assess clinical outcomes. This manuscript reviews the state of the art in acute stroke therapy.