This Annals volume presents work from leading and emerging investigators from within and outside the immediate area of cerebrovascular disease. These short reviews explore the state-of-the-art and future directions of research and clinical practice leading to enhanced medical care in the acute treatment of ischemic stroke. Papers in this volume highlight various facets of acute intervention and issues related to the medical setting for stroke that affect clinical outcomes and provide opportunities for improving treatment. Collectively, this volume examines the generation of data-driven, multidisciplinary ideas to explore ischemic stroke as a systemic disease related to other disease entities (hypertension, diabetes, and disorders of aging), and to better address the evolution of ischemic brain injury.