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Recombinant human erythropoietin (rHuEPO) and iron supplementation have had a profoundly positive impact on the anemia of patients with chronic kidney disease. However, a significant number of patients remain hyporesponsive to rHuEPO, with hemoglobin values less than target levels. A suboptimal response to rHuEPO is associated with complications that can reduce quality of life and increase morbidity, mortality, and costs. There are a number of other metabolic derangements associated with uremia that can impact on the production and survival of red blood cells. Dialysis-related carnitine disorder is a functional metabolic deficiency, common in chronic dialysis patients, that can have a negative impact on erythrocyte production and survival. This article reviews the role of L-carnitine in the pathogenesis and adjunctive treatment of anemia associated with kidney failure. After a comprehensive database search, primary and secondary reports were analyzed. Laboratory studies examining the influence of carnitine on red blood cell function and clinical trials of L-carnitine in dialysis patients support the use of L-carnitine in the setting of rHuEPO hyporesponsiveness. Consensus groups, including the National Kidney Foundation-Kidney Disease Outcome Quality Initiative (K/DOQI), consider the use of L-carnitine for hyporesponsive rHuEPO-dependent anemia a promising application of this therapy, recommending an empiric trial of L-carnitine in these patients.