Chronic heart failure (CHF) is a complex clinical syndrome leading to exercise intolerance due to muscular fatigue and dyspnea. Hemodynamics fail to explain the reduced exercise capacity, while a significant skeletal muscular pathology seems to constitute the main underlying mechanism for exercise intolerance in CHF patients. There have been proposed several metabolic, neurohormonal and immune system abnormalities leading to an anabolic/catabolic imbalance that plays a central role in the pathogenesis of the wasting process of skeletal muscle myopathy. The impairment of the anabolic axes is associated with the severity of symptoms and the poor outcome in CHF, whereas increased cortisol levels are predictive of exercise intolerance, ventilatory inefficiency and chronotropic incompetence, suggesting a significant contributing mechanism to the limited functional status. Exercise training and device therapy could have beneficial effects in preventing and treating muscle wasting in CHF. However, specific anabolic treatment needs more investigation to prove possible beneficial effects.