Chronic heart failure (CHF) is a condition characterized by exercise intolerance. The level of activity tolerated by an individual cannot be predicted by classical parameters of left ventricular performance. Therefore, considerable attention has been focused on the role of peripheral factors such as skeletal muscle, which are determinants of work capacity. In recent years, many alterations in the skeletal muscle have been described in patients with chronic heart failure. This knowledge has dramatically changed the treatment of patients with CHF. Previously, patients were asked to avoid excessive strain and physical exercise. Recently, however, patients are asked to participate in a supervised physical training program to increase their exercise capacity and to counteract the molecular changes occurring in the skeletal muscle. This review will focus on molecular and biochemical alterations especially in the skeletal muscle and how these alterations are influenced by exercise training finally contributing to better skeletal muscle performance.