In vitro studies of cerebrospinal fluid indicate that normal cerebrospinal fluid contains very low levels of fibrinolytic enzymes but that fibrinolytic activity is higher in pathologic compared with normal conditions and in older compared with younger patients. Because of the low endogenous fibrinolytic activity of the central nervous system, intraventricular fibrinolytic therapy has been studied in adult and pediatric patients for the treatment of intraventricular hemorrhage/post-hemorrhagic hydrocephalus and subarachnoid hemorrhage with secondary cerebral vasospasm. A review of the literature about endogenous and exogenous fibrinolysis studies of animals, adult humans, and pediatric humans reveals a record of predominant safety and efficacy. Although its use in the adult population for the treatment of subarachnoid hemorrhage with secondary vasospasm has become an accepted therapy in some centers, its use in the pediatric population is less common. It is no longer considered in the treatment of meningitis, but its role in the treatment of intraventricular hemorrhage/posthermorrhagic hydrocephalus is still being investigated.