Protein wasting (PW) or protein-energy wasting (PEW) occurs commonly in patients with diabetes mellitus who have end-stage renal disease (ESRD) and are undergoing maintenance dialysis (MD) therapy. Some but not all studies indicate that PW or PEW is more prevalent in diabetic when compared with nondiabetic MD patients and that diabetic patients commencing maintenance hemodialysis (MHD) are more likely to lose fat-free, edema-free weight than are incident nondiabetic MHD patients. The causes of PW and PEW in diabetic MD patients are probably largely similar to those of nondiabetic MD patients. These causes include anorexia, reduced food intake, concurrent illnesses particularly when associated with inflammatory processes, physical or mental debility, removal of nutrients by dialysis procedure, acidemia, possibly physical deconditioning, and oxidant and carbonyl stress. However, diabetic MD patients are also at greater risk for PW or PEW from comorbidities related to diabetes per se. These disorders include ischemic vascular disease, hypertension, gastrointestinal dysfunction, and neuropathy. Metabolic disorders such as insulin deficiency or resistance to the actions of insulin, and elevated levels of counterregulatory hormones may also contribute to PW or PEW in diabetic MD patients. Mechanisms by which these metabolic disorders in diabetic ESRD patients may cause PW or PEW are discussed.