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Perinatal brain injury is a major cause of neurological disability in both premature and term infants. In this review, we summarize the evidence behind some established neuroprotective practices such as administration of antenatal steroids, intrapartum magnesium for preterm delivery, and therapeutic hypothermia. In addition, we examine emerging practices such as delayed cord clamping, postnatal magnesium administration, recombinant erythropoietin, and non-steroidal anti-inflammatory agents and finally inform the reader about novel interventions, some of which are currently in trials, such as xenon, melatonin, topiramate, allopurinol, creatine, and autologous cord cell therapy.