Patients with end-stage renal disease (ESRD) commonly present both anorexia (defined as reduced apetite) and a catabolic state leading to loss of protein from skeletal muscle and other tissues. Additionally, these patients carry an inflammatory burden, which may play a pivotal role in the evolution of not only the observed cachexia, but also in the massive increase in relative risk of cardiovascular disease (CVD) in this population. Evidence suggests that a facilitative interaction between pro-inflammatory cytokines and other factors, including central nervous system regulation of appetite, co-morbidies, acidosis, anaemia and hormonal derangements combine to produce both anorexia and cachexia in this patient group. So far, interventional therapies have failed to significantly alleviate the cachexic state in ESRD, presumably because of the need to attack other causative factors. Therefore, new treatment strategies such as multiple appetite stimulants, various “anti-inflammatory diets” and new potentially useful anti-inflammatory pharmacological agents should be tested alone or in combination to evaluate if these new therapeutic modalities could improve the poor outcome of ESRD patients. As the etiology of cachexia in ESRD is multifactorial, we propose that its treatment should comprise a number of concomitant therapies to provide an integrated strategy aiming to reverse this devastating complication.