Recombinant human erythropoietin (r-HuEPO; epoetin alfa) is well established as safe and effective for the treatment of anemia. In addition to the erythropoietic effects of endogenous erythropoietin (EPO), recent evidence suggests that it may elicit a neuroprotective effect in the central nervous system (CNS). Preclinical studies have demonstrated the presence of EPO receptors in the brain that are up-regulated under hypoxic or ischemic conditions. Intracerebral and systemic administration of epoetin alfa have been demonstrated to elicit marked neuroprotective effects in multiple preclinical models of CNS disorders. Epoetin alfa has also been shown to prevent the loss of autoregulation of cerebral blood flow in a model of subarachnoid hemorrhage. The mechanisms of EPO-induced neuroprotection include prevention of glutamate-induced toxicity, inhibition of apoptosis, anti-inflammatory effects, antioxidant effects, and stimulation of angiogenesis. Collectively, these findings suggest that epoetin alfa may have potential therapeutic utility in patients with ischemic CNS injury.