Cardiac resynchronization therapy (CRT) addresses abnormal left ventricular (LV) activation that produces detrimental effects on cardiac systolic and diastolic function. CRT improves symptoms and ventricular performance, promotes reverse remodeling, and decreases mortality and hospitalization in patients with congestive heart failure (CHF). Atrial-synchronized biventricular stimulation reverses many of the temporal delays in mechanical activation associated with LV dysfunction and conduction system disease. The therapy evolved from anecdotal application through surgical implantation of LV pacing leads to transvenous delivery of LV pacing leads for use with dedicated CRT devices. The controlled clinical trials included specific patient groups, and provided data leading to widely adopted indications for the therapy. Current indications exclude the use of CRT in patients with permanent atrial fibrillation, although small series suggest a benefit of the therapy in these patients. The role of cardiac imaging with echocardiography to detect cardiac dyssynchrony promises to improve patient selection by not only excluding likely nonresponders, but also extending the therapy to those with dyssynchrony in the absence of QRS prolongation. Expanded indications under evaluation include the role of CRT in patients with mildly symptomatic CHF, mild to moderate LV dysfunction, dyssynchrony in the absence of QRS prolongation, and dyssynchrony induced by right ventricular pacing.