Cardiac resynchronization therapy is an established treatment modality in heart failure. Though non-response is a serious issue. To address this issue, a good understanding of the electrical activation during left bundle branch block, biventricular, as well as right- and left ventricular pacing is needed. This way by interpreting the 12-lead electrocardiogram, possible reasons for suboptimal treatment can be identified and addressed. This article reviews the literature on QRS morphology in cardiac resynchronization therapy and its meaning in optimization of therapy.