Uremic malnutrition, as evidenced by decreased muscle mass, is strongly associated with increased risk of death and hospitalization events in chronic hemodialysis (CHD) patients. Several factors that influence protein metabolism predispose CHD patients to increased catabolism and loss of lean body mass. It has been long suspected that the hemodialysis (HD) procedure is a net catabolic event. Recent studies show that the HD procedure indeed induces a net protein catabolic state at the whole-body level as well as in skeletal muscle. There is evidence to suggest that these undesirable effects are caused by decreased protein synthesis and increased proteolysis. Animal studies suggest that decreased protein synthesis is likely mediated by the significant decrease in plasma amino acid concentrations during HD. On the other hand, increased protein degradation is, at least in part, mediated by the HD-associated inflammatory response.