Cardiac resynchronization therapy (CRT) is an integral component of modern heart failure therapy for patients with severe symptoms (New York Heart Association [NYHA] class III or IV), a reduced ejection fraction (≤ 35%), and a wide QRS complex (> 120 ms). Results from recent trials have provided ample evidence that CRT may also reduce morbidity and mortality in patients with mildly symptomatic heart failure (NYHA class II). As a result, the 2010 European guidelines now recommend CRT for this patient population (level of evidence I, class A). This review summarizes and critically evaluates the landmark Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE), Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT), and Resynchronization/Defibrillation for Ambulatory Heart Failure Trial (RAFT) studies, which comprise the suite of randomized controlled trials available today on this matter. Furthermore, we discuss the rationale and available evidence for other emerging indications for CRT, including its use in patients with a mildly reduced left ventricular ejection fraction (> 35%), in those with a narrow QRS complex (≤ 130 ms), or in patients with concomitant bradyarrhythmic pacemaker indications.