Although the additional therapies with beta-blockers and spironolactone have recently proved to be significantly beneficial for the treatment of advanced heart failure, in the end stages of this disease the prognosis remains quite poor. Moreover, the quality of life of patients with advanced heart failure is still heavily influenced by symptoms and by a high rate of hospitalizations. In selected patients heart transplantation constitutes the only chance, but the low availability of donors limits a wider diffusion of this procedure. Mechanical left ventricular assistance is still considered a bridge to heart transplantation and, at present, technical reasons limit the long-term utilization of these devices. Xenotransplantation and regeneration of cardiac myocytes from bone marrow stem cells remain the greatest hopes for the future. Several other possibilities of offering broader opportunities to patients with end-stage heart failure are under investigation. The expectations regarding the antagonism of cytokines and endothelin were not confirmed by the recent results of several studies. The association between beta-blockers and non-adrenergic inotropes could have a rationale, but needs to be investigated with appropriate trials. Other surgical procedures, such as myocardial revascularization in case of severe ischemic left ventricular dysfunction or repair of severe secondary mitral regurgitation, represent surgical options the use of which may be more widespread, but their indications are still based on a rather empirical approach. The preliminary results of the electrical therapy of ventricular resynchronization are encouraging, but the selection of patients and the long-term advantages need to be defined further on. Moreover, advanced heart failure has a major impact on health costs and organization. This makes mandatory the definition of operative hospital- and home-care models, the use of which in clinical practice is to be proposed.