Chronic heart failure is one of the major health care issues in terms of increasing number of patients, rate of hospitalizations and costs. Heart transplantation is the best established therapy for patients with severe heart failure. However, the number of donors limits the activity to 5000 heart transplants performed annually worldwide. This limitation has generated alternative treatments. The increase of the interest in the reversibility of the heart failure and the application of new biological alternatives has generated therapeutic strategies designed to integrate biology and medical technologies in order to act to the biomechanical, the molecular and the neurohormonal mechanisms of heart failure. These treatments include cellular cardiomyoplasty, tissue engineering, surgical left ventricular restoration as well as passive and active mechanical ventricular assistance as destination therapy, bridge to recovery or bridge to transplantation. The integrated development of these approaches could offer hopeful treatments, although there is still much to be learned regarding the optimal use of these strategies.