This review aims to provide a synthesis of the published evidence regarding the rationale and clinical benefits of cardiac resynchronization therapy (CRT) with implantable atrial-synchronized biventricular pacing (BVP) devices in patients with moderate to advanced heart failure and intra- and interventricular conduction delays. In addition, it addresses clinical and technical issues that have yet to be resolved, such as the selection of the most suitable candidates for CRT; the usefulness of combining BVP with automatic defibrillation backup; the value of CRT in patients with atrial fibrillation; the importance of alternative sites of pacing, such as the atrial septum and the right ventricular (RV) outflow tract; the harmful effects of the long-standing practice of producing an iatrogenic left bundle branch block by conventional RV pacing in patients receiving standard permanent pacemakers; the question of precisely where on the left ventricle optimal pacing is achieved; and the potential applications of CRT in patients with pediatric or congenital heart disease. Considering how major advances have been achieved since the first clinical application of CRT in 1994, one can be optimistic about the future of the electrotherapeutic management of heart failure.