Reduced aerobic capacity, as measured by maximal oxygen uptake, is a hallmark in cardiovascular diseases and strongly predicts poor prognosis and higher mortality rates in heart failure patients. While exercise capacity is poorly correlated with cardiac function in this population, skeletal muscle abnormalities present a striking association with maximal oxygen uptake. This fact draws substantial attention to the clinical relevance of targeting skeletal myopathy in heart failure. Considering that skeletal muscle is highly responsive to aerobic exercise training, we addressed the benefits of aerobic exercise training to combat skeletal myopathy in heart failure, focusing on the mechanisms by which aerobic exercise training counteracts skeletal muscle atrophy.