Cardiac resynchronization therapy (CRT) is an important therapy for heart failure patients with prolonged QRS duration. In patients with left bundle branch block the altered left ventricular electrical activation results in dyssynchronous, inefficient contraction of the left ventricle. CRT aims to reverse these changes and to improve cardiac function. This article explores the electrophysiologic and hemodynamic changes that occur during CRT in patient and animal studies. It also addresses how novel techniques, such as multipoint and endocardial pacing, can further improve the electromechanical response.