Skeletal myopathy plays a prominent role in heart failure (HF) symptoms since skeletal muscle myopathy worsens with HF progression and parallels exercise intolerance observed in HF individuals. HF-induced skeletal muscle myopathy includes morphological and functional changes along with derangements in skeletal muscle metabolism and autonomic function. We have demonstrated that autonomic dysfunction, such as sympathetic hyperactivity, contributes to the skeletal myopathy in HF. Mice with sympathetic hyperactivity-induced HF (Brum et al 2002) display skeletal myopathy characterized by exercise intolerance, skeletal muscle pro-oxidant state (marked by decreased redox balance and increased lipid hydroperoxidation) and skeletal muscle wasting (Bacurau et al 2009, Bueno et al 2010). The latter is associated with increased proteolysis by the ubiquitin-proteasome system (Cunha et al 2012). Aerobic exercise training is a powerful tool counteracting skeletal muscle myopathy. We have observed reduced muscle noradrenaline levels and oxidative stress associated with improved exercise capacity and re-established muscle mass in HF (Bacurau et al 2009). The mechanism by which aerobic exercise training prevents/attenuates skeletal muscle atrophy is unclear. Recent data from our group suggest that aerobic exercise training improves protein synthesis by increasing skeletal muscle IGF-1/PI3K/Akt signaling pathway in HF mice (Bacurau et al, unpublished results). Interestingly, we have also demonstrated that aerobic exercise training reduces protein catabolism. Aerobic exercise training decreased mRNA levels of the main skeletal muscle atrophic genes (MuRF and Atrogin-1/MAFbx) and reestablished proteasome activity in both mice and humans with HF (Cunha et al 2012). Collectively, our studies suggest that aerobic exercise training promotes remarkable adaptations in skeletal muscle in HF that counteract skeletal myopathy. Regarding skeletal muscle wasting, aerobic exercise training prevents atrophy leading to a better balance between protein synthesis and degradation. Therefore, aerobic exercise training is a powerful non-pharmacological therapy for HF.