Studies show that erythropoietin, besides its critical role in hematopoiesis, provides neuroprotection in hypoxic-ischemic cerebral injury. Antiapoptotic, anti-inflammatory, angiogenetic, and neurotrophic properties of erythropoietin could increase indications, currently restricted to anemia in chronic renal failure and cancer, to hypoxic-ischemic cerebral insult. In the adult and neonatal animal model of hypoxic-ischemic cerebral injury, erythropoietin significantly reduces infarct size with attenuation of brain damage, and preservation of cortical integrity. The first human study on the impact of erythropoietin in stroke victims showed that erythropoietin is safe and well tolerated at high doses, and associated with improved neurological outcome. Even with intravenous application, concentrations of erythropoietin in cerebrospinal fluid of these patients were many-fold higher than in non-treated patients. In successfully resuscitated cardiac arrest victims overall neurological recovery remains poor despite improved cardiopulmonary resuscitation strategies. Post-resuscitation care needs further advances in order to improve final outcome. Through promotion of neuroangiogenesis, inhibition of hypoxia-induced apoptosis in neurons, and thus support of the survival of neurons in the ischemic brain, erythropoietin could be used to improve functional recovery of these patients. Nevertheless, optimal molecular forms of EPO, therapeutic doses, and treatment time window have to be determined in order to lower the incidence of adverse effects and still preserve neuroprotective properties.