Heart failure is a constantly progressing disease involving patients with ischemic and nonischemic cardiac disease. Cardiac resynchronization therapy (CRT) has been used successfully in patients with severe heart failure symptoms, poor left ventricular (LV) function, and a prolonged QRS duration. Large trials in patients with New York Heart Association (NYHA) class III/IV heart failure have demonstrated that heart failure symptoms can be reduced and exercise capacity improved, overall mortality decreased, and ventricular function increased. How long these beneficial effects of CRT will last in patients with an already advanced stage of heart failure, particularly in NYHA IV, is still unknown. Therefore, it is more reasonable to initiate CRT in appropriate patients who have structural heart disease but have not yet developed severe heart failure symptoms. Slowing heart failure progression seems to be the most important target. Medical treatment alone has not demonstrated that this can be achieved in patients with poor ventricular function and prolonged QRS (>120 ms). The recently published results of MADIT-CRT, as well as the extended follow-up of the REVERSE substudy of the European patient cohort, have shown that prevention of heart failure progression can be well accomplished with CRT and implantable cardioverter–defibrillator (ICD) backup (CRT-D). Heart failure events and death occurred significantly less often in patients with CRT-D than in those with an ICD only. A clinically important reversal of ventricular remodeling with reduced ventricular volumes and increased LV ejection fraction was found in the CRT-D–treated patients. The benefit was seen in patients with ischemic and nonischemic cardiomyopathy and in those with NYHA class I or II heart failure; the most benefit was demonstrated in patients showing a “classic” left bundle branch block electrocardiogram pattern (about 70% of the enrolled patients) and in female patients. Results from both trials support the view that future efforts regarding heart failure treatment should concentrate more on prevention of heart failure progression in mildly symptomatic or even asymptomatic candidates for CRT-D. It is time to change the guidelines for heart failure treatment.