Cachexia is a pathological state characterized by weight loss and protein mobilization during various diseases. Nutritional supplementation or appetite stimulants are unable to restore the loss of lean body mass. Agents interfering with TNF-alpha have not been very successful to date. Only eicosapentaenoic acid was able to interfere with the action of proteolysis-inducing factors. An acceleration of proteolysis and branched-chain amino acid oxidation was correlated with chronic metabolic acidosis. Therefore, we suggest here that the main cause of cachexia is the increased acidity of the body fluids, which results in a higher and non-specific proteolysis of muscle proteins. Moderate hypoxia might be close related to lactic acid production within the whole body, not only in the cancer cells. Anorexia seems to be a consequence, but a cause of cachexia: the cachectic patients are in fact well fed, unfortunately they use fatty acids from their fat and glucose via muscle proteins, amino acids, alanine, and lactic acid. Our hypothesis is consistent with the most findings reported in literature and opens new ways for cachexia prevention and therapy, such as pH correction or higher oxygenation.