Nutritional status is an important predictor of clinical outcome in end-stage renal disease (ESRD) patients, especially in patients on chronic hemodialysis. Uremic malnutrition is strongly associated with increased risk of death and hospitalization events in this patient population, and decreased muscle mass is the most significant predictor of these outcomes. Several factors that influence protein metabolism predispose chronic hemodialysis patients to increased catabolism and loss of lean body mass. The available evidence suggests that low protein and energy intake associated with advanced uremia along with catabolic consequences of dialytic therapies can lead to the development of uremic malnutrition. Recent studies show that the hemodialysis procedure induces a net protein catabolic state at the whole-body level as well as skeletal muscle. There is evidence to suggest that these undesirable effects are due to decreased protein synthesis and increased proteolysis. Provision of nutrients, either in the form of intradialytic parenteral nutrition or oral feeding during hemodialysis, can adequately compensate for the catabolic effects of the hemodialysis procedure. While the mechanisms of these effects are not studied in detail, changes in extracellular amino acid concentrations, along with certain anabolic hormones such as insulin, are important mediators of these actions.