Cardiac resynchronization therapy (CRT) has become a standard of care for symptomatic heart failure patients with reduced left ventricular ejection (LVEF) in the setting of electrical conduction disease. Successfully delivered CRT corrects left ventricular electromechanical dyssynchrony resulting in LVEF increase, reverse remodeling, improved quality of life, and better survival. The development of conduction system pacing during the last decade has emerged as an alternative and complementary technique to classic CRT. In the following chapter we will analyze the pathophysiology of dyssynchrony and dyssynchrony assessment, the extent of clinical evidence in cardiac resynchronization therapy, the issue of non-response to CRT, how to improve patient selection and CRT delivery, as well as the role of conduction system pacing for CRT according to clinical evidence and current guidelines.