Cardiac resynchronization therapy (CRT) is a new non-pharmacological option for patients with advanced heart failure and ventricular conduction delay. Four randomized prospective studies have provided evidence that CRT increases exercise capacity, improves functional class and quality of life. There is also increasing evidence that CRT may trigger an inverse remodeling process leading to reduction of ventricular diameter and eventually of the atrial size. The pathophysiological mechanism throughout CRT may promote inverse remodeling is: (1) reduction of systolic and diastolic mitral regurgitation; (2) reduction of sympathetic/parasympathetic imbalance as well as reduction of neurohumoral activation due to increased systolic blood pressure and improved filling time; (3) reduction of regional wall stress. The structural changes taking place during CRT are directly related to continuous pacing, because lack of pacing immediately shows the new onset of remodeling. The duration of the reported changes of ventricular diameter is still unknown, and it is also unknown whether such reverse remodeling process of the ventricle and of the atria will lead to a reduction of cardiac death and incidence of ventricular arrhythmias.