Newborns comprise the largest group of children developing thromoboembolic events (TE(S)), due to the peculiarities of their developmental hemostatic system. Moreover, in the sick newborn, especially preterm, numerous acquired perinatal and iatrogenic conditions might result in a disturbance between coagulation and fibrinolysis, leading to thrombus formation. Nevertheless, the contribution of acquired prothrombotic disorders in the pathogenesis of thromboembolic disease in newborns remains poorly defined. Few data are currently available regarding the influence of maternal or fetal genes on thrombotic risk in the fetus and neonate. Ongoing National and International registries are partially answering these questions. The purpose of this review is to evaluate the current knowledge about the role of inherited, acquired perinatal and maternal prothrombotic risk factors in neonatal cerebral nervous system (CNS) thrombotic events and non-CNS thrombotic events.