The progression of the aging process leads to a decreased margin of homeostatic reserve and a reduced ability to accommodate metabolic challenges, including nutritional stress. Nutritional frailty refers to the disability that occurs in old age owing to rapid, unintentional loss of body weight and loss of lean body mass (sarcopenia). Sarcopenia, a loss of muscle mass and strength, contributes to functional impairment. Weight loss is commonly due to a reduction in food intake; its possible etiology includes a host of physiological and nonphysiological causes. The release of cytokines during chronic disease may also be an important determinant of frailty. In addition to being anorectic, cytokines also contribute to lipolysis, muscle protein breakdown, and nitrogen loss. Whereas the multiple causes of nutritional frailty are not completely understood, clinical interventions for weight loss, sarcopenia, and cytokine alterations have been used with modest success.