Cardiac resynchronization therapy is an established treatment for patients with severe heart failure and ventricular conduction disturbance. Cardiac resynchronization therapy improves cardiac pump function and clinical status, and reduces morbidity and mortality. This electrical treatment for heart failure has also contributed enormously to the understanding of the pathophysiology of ventricular conduction disturbance. This article highlights the latest findings about the pathophysiology of ventricular conduction disturbance and pacing as well as that of resynchronization, with emphasis on the role of regional mechanical performance in triggering remodeling processes involved and on the selection of patients using mechanical dyssynchrony.