Left bundle branch block (LBBB), traditionally viewed as an electrophysiologic abnormality, is increasingly recognized for its profound hemodynamic effects. LBBB causes asynchronous myocardial activation, which, in turn, may trigger ventricular remodeling. Exercise nuclear studies frequently show reversible perfusion defects in the absence of obstructive coronary artery disease and some patients with intermittent LBBB develop angina coincident with the onset of LBBB. It is uncertain, however, if these phenomena are because of myocardial ischemia or ventricular asynergy. LBBB is associated with impaired systolic and diastolic function. In patients with dilated cardiomyopathy (DCM), LBBB is accompanied by progressive left ventricular (LV) dilatation and mitral regurgitation. It is not known whether LBBB is the cause or the consequence of LV dilatation. DCM patients with LBBB, as compared to those with normal intraventricular conduction, are more likely to have a nonischemic etiology, profound LV dilatation, lower ejection fraction, increased symptomatology, and shorter survival. Patients with DCM and acceleration-dependent LBBB may benefit from restoration of a narrow QRS complex by suppressing the heart rate with beta-blocker. There is extensive research underway in patients with DCM and LBBB to evaluate the short and long-term effects of normalization of ventricular activation sequence with high septal, LV, or biventricular pacing.