Arterial ischemic stroke (AIS) is a rare disorder in children. Research suggests that risk factors, outcomes, and presentation are different from those of adult stroke. In particular, prothrombotic abnormalities and large vessel arteriopathies that are nonatherosclerotic seem to play a large role in the pathogenesis of childhood AIS. This review examines the epidemiology and etiologies of neonatal and childhood AIS and provides a detailed discussion of approaches to the clinical characterization, diagnostic evaluation, and management. Long-term outcomes of recurrent AIS and neuromotor, speech, cognitive, and behavioral deficits are considered. Emphasis is on evidence underlying current knowledge and key questions for further investigation.