Carnitine is mainly biosynthesized in the liver and kidneys, and free carnitine is reabsorbed by renal tubules, so that carnitine deficiency and insufficiency frequently occur in end-stage renal failure patients. Kidney has mainly three functions: filtration at glomerulus, reabsorption at tubules, and secretion at interstitium of various factors such as erythropoietin. Dialysis process includes hemodialysis and peritoneal dialysis replaces only filtration function; it does not replace reabsorption and secretion functions. Continuous renal replacement therapy also causes severe carnitine deficiency. In these renal failure patients, not only reduced free carnitine, but also accumulation of acylcarnitine is observed resulting in carnitine insufficiency (high acylcarnitine concentration/free carnitine concentration (AC/FC)) which inhibits mitochondrial functions. Carnitine deficiency and insufficiency cause various symptoms such as erythropoiesis-stimulating agent (ESA)-resistant anemia, muscle symptoms such as severe muscle cramps and asthenia, cardiac hypertrophy, arrhythmias, cardiac disfunctions, and increased inflammation, malnutrition, and sarcopenia. Patients with renal failure are sometimes recommended to restrict protein intake which might also accelerate carnitine deficiency. Although there are controversies about carnitine supplementation to end-stage renal failure patients, many clinical studies indicate usefulness carnitine supplementation therapy. Detailed mechanisms of effects of carnitine in these patients are explained in this chapter.