Since the first application of cardiac resynchronization therapy (CRT) in 1994, an important body of information has been delivered from many randomized trials including a large number of patients. Most of these trials have showed strong evidence to support the use of CRT to improve heart failure symptoms, quality of life, left ventricular ejection fraction, exercise capacity and survival. As a result, current guidelines recommend the use of CRT as a Class I indication in patients with NYHA classes III or IV, LVEF less than 35%, QRS duration greater than120 ms, LV end-diastolic diameter > 55 mm and, sinus rhythm. However, a lack of information exists regarding other scenarios such as patients in NYHA classes II, patients with a narrow QRS complex, patients with normal ejection fraction or patients with baseline rhythms other than sinus rhythm such as those in atrial fibrillation or pacing dependent. The following chapter is dedicated to the indications for CRT therapy recommended on current clinical guidelines from the American and European Societies reviewing the clinical evidence supporting these indications.