Uremic malnutrition is highly prevalent and is associated with poor clinical outcomes in end-stage renal disease (ESRD) patients. Inadequate diet and a state of persistent catabolism play major roles in predisposing these patients to uremic malnutrition and appear to have an additive effect on overall outcome. Recent studies highlight the existence of a complex syndrome involving chronic inflammation, metabolic abnormalities, and hormonal derangements contributing to the increased morbidity and mortality observed in ESRD patients. Novel strategies such as appetite stimulants, anti-inflammatory drugs, and anabolic hormones along with conventional nutritional supplementation may provide potential interventions to improve clinical outcome in ESRD patients.