Skeletal muscles, such as the latissimus dorsi muscle, can be transformed to gain considerable fatigue resistance to be suitable either for cardiomyoplasty, or to power a cardiac assist device. Such transformation of the skeletal muscle can be achieved by low frequency electrical stimulation for several weeks. In this article, we reviewed the stimulation protocol, and subsequent histochemical, biochemical, and functional changes in the skeletal muscle, and compared them to those of the cardiac muscle. The parameters that should be useful for stimulating such a muscle to assist the heart are defined. The issues currently under study, including the optimal transformation parameters, the feasibility of working transformation, and the importance of device design to minimize vascular compromise of the muscle, are also discussed. It is concluded that there is a great potential to use the plasticity of skeletal muscle for clinical purposes, specifically by transforming the skeletal muscle to resemble the myocardium in order to use it either to replace or repair the myocardium, or as the endogenous power source for a cardiac assist device.