Despite the improvement in pharmacologic treatment of heart failure, many patients continue to have severe persistent symptoms, and their prognosis remains poor. One of the most recent advances in heart failure management is the concept of cardiac resynchronization therapy (CRT) with right and left ventricular pacing. Large clinical trials have demonstrated morbidity and mortality benefits of CRT in patients with moderate to severe drug refractory heart failure (New York Heart Association (NYHA) functional class III or IV), and ejection fraction < or = 35% with QRS duration > or = 120 ms. Despite the documented benefits, 20-30% of patients selected to have CRT do not respond to this treatment. Echocardiography will probably play a more important role in better selecting patients with mechanical dyssynchrony who are more likely to respond to CRT. This article reviews the available evidence for CRT as well as the way to select responders to this rather invasive therapy.