Cardiac transplantation still remains the only radical treatment of end-stage heart failure but organ shortage results in the lengthening of the waiting period during which hemodynamic decompensation may occur and then require temporary circulatory support. Improvement in these assist devices now allows to permanently implant some of them which then appear as true alternatives to cardiac transplantation when this technique is contra-indicated. In parallel to these "mechanical" options, "biological" strategies have been designed, which are primarily based on cell therapy. Thus, autologous skeletal myoblast transplantation has yet entered the clinical arena, on the basis of experimental data suggesting the functional efficacy of these cells once implanted into infarcted myocardium. However, the clinical benefits of this approach still need to be validated by randomized trials. Gene therapy appears more complex to implement clinically, because of the multiplicity of candidate genes and the persisting issues associated with vectors and gene transfection systems.