Protein energy wasting is common in patients with CKD and ESRD and is associated with adverse clinical outcomes, such as increased rates of hospitalization and death, in these patients. A multitude of factors can affect the nutritional and metabolic status of patients with CKD, including decreased dietary nutrient intake, catabolic effects of renal replacement therapy, systemic inflammation, metabolic and hormonal derangements, and comorbid conditions (such as diabetes and depression). Unique aspects of CKD also confound reliable assessment of nutritional status, further complicating management of this comorbid condition. In patients in whom preventive measures and oral dietary intake from regular meals cannot help them maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is effective in replenishing protein and energy stores. The advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic steroids and exercise, with nutritional supplementation or alone, improve protein stores and represent potential additional approaches for the treatment of PEW. There are several emerging novel therapies, such as appetite stimulants, anti-inflammatory interventions, and anabolic agents.