Recombinant human erythropoietin (rHuEPO) has received considerable attention as a potential transfusion sparing strategy in the ICU. Interestingly, EPO and its receptor are both expressed by the nervous system, and systemically administered rHuEPO can reach sites within the brain. In preclinical studies, rHuEPO reduced neuronal injury produced by focal ischemia, TBI, spinal cord injury, and subarachnoid hemorrhage [96] [97] [98] . Enthusiasm regarding its use as a general neuroprotectant in the ICU has been tempered by potential risks such as thromboembolism and the considerable cost of the drug. Concerns over safety may be at least partially addressed by the recent finding of erythropoietin derivatives with tissue protective but not hematopoietic properties [99] .