Perinatal ischemic stroke is not rare in term and near-term infants and is an important antecedent of long-term neurological disability, including congenital hemiplegia (hemiplegic cerebral palsy) and seizure and cognitive disorders. Changes in maternal hemostasis occur in pregnancy and are amplified in the period immediately surrounding birth; stroke and other thromboembolic events are more frequent in both mother and infant in this period. The vasculature and hemostatic mechanisms of placenta as well as brain are likely to be important in the pathobiology of perinatal stroke. Maternal and infant thrombophilias, genetic and acquired, play a role. Rarely is >1 child in a sibship affected, and environmental factors—substantially less studied, to date—are likely to be key determinants of risk.