L-carnitine plays an essential role in the beta-oxidation of fatty acids by catalyzing their transport into the mitochondrial matrix. The kidney maintains plasma free L-carnitine levels in the homeostatic range by selective saturable tubular reabsorption. The preferential retention of free L-carnitine over acyl-L-carnitines by the kidney is lost in patients with end-stage renal disease (ESRD). Loss of renal parenchyma as a site of carnitine synthesis, as well as nonselective clearance of L-carnitine by the dialysis procedure lead to dialysis-related carnitine deficiency. Numerous studies investigating whether L-carnitine supplementation will alleviate several dialysis-related symptoms, such as intradialytic hypotension, heart failure, muscle weakness, low exercise capacity, and anemia, have reported conflicting results. Many of these studies suffer from a lack of randomization and control groups, heterogeneity in the administration of L-carnitine, and nonstandardized measures of symptom improvement. More data exist to support the use of L-carnitine in selected anemic dialysis patients with very large erythropoietin requirements in whom extensive examination for reversible causes of anemia was unrevealing.