Mechanical assist devices have been used increasingly to support patients who await heart transplantation. The initial goal was to provide sufficient circulatory function to keep these patients alive and to allow them to recover from secondary organ dysfunction. A recent observation showed an improvement in native heart performance in some transplant candidates who receive support with mechanical assist devices. Under these conditions, myocardial recovery has been mostly restricted to patients with primary dilated cardiomyopathy and with extended periods of ventricular support. Also, the exact mechanisms that lead to substantial myocardial recovery remain unknown. Several investigations have demonstrated improved myocyte performance, reduced fibrosis, reduced cytokine levels, and reduced autoantibodies during long-term mechanical support; therefore, the observation of cardiac recovery during mechanical support is in accordance with currently discussed models of end-stage heart failure.