Prothrombotic disorders are believed to be important contributors to the etiology of peri- and neonatal arterial ischemic stroke and sinovenous thrombosis, which may lead to life-long disability. This article reviews hematological issues unique to the perinatal period, including: the significance of the placenta as the interface between maternal and fetal circulations; normal changes in the coagulation system of mothers during and just after gestation; and the significance of prothrombotic disorders in the mother and/or fetus. Other possible maternal and neonatal contributors to peri- and neonatal stroke are discussed, including: infection, pre-eclampsia, diabetes, and drug use in the mother; and infection, dehydration, complex congenital heart disease, extracorporeal membrane oxygenation, and catheter placement in the neonate. Possible approaches to preventing and treating perinatal and neonatal stroke are presented.