The problem of perinatal brain injury, in terms of the costs to society and to the affected individuals and their families, is extraordinary. The most common underlying cause of perinatal brain injury is hypoxia/ischemia. Intrauterine hypoxia and birth asphyxia induced brain damage are associated with increased perinatal mortality and long term sequelae of neurodevelopmental compromise, seizures disorders and cerebral palsy. The roles of ROS, Ca2+, NMDA receptors, excitatory amino acids, and apoptotic genes on fetal brain injury have been studied exclusively. These works have led to substantial conceptual agreement on a general outline of how fetal brain injury triggers and evolves to produce neuropathologic lesions and neurodevelopmental disabilities. However, the precise etiological factors for the development of the majority of fetal hypoxic brain injury have not been identified satisfactorily. We initially indicated that multiple pathways involved in the fetal brain injury mediated by chronic hypoxia.