The beneficial effects of cardiac resynchronization therapy (CRT) on morbidity and mortality in advanced heart failure patients have been extensively demonstrated. However, previous single- and multicenter studies demonstrated that approximately 30-40% of CRT patients do not show significant clinical improvement or LV reverse remodeling despite fulfilling current inclusion criteria. In search of novel indices that may help to improve the selection of responders to CRT, non-invasive multimodality imaging has provided further insight into the mechanisms underlying CRT response. LV dyssynchrony, extent and location of myocardial scar and LV lead position have shown to be independent determinants of CRT response. An integrated evaluation of these three pathophysiological mechanisms may provide a more accurate selection of heart failure patients who will benefit from CRT and may maximize the cost-effectiveness of this therapy. The present review article provides a critical appraisal of the role of multimodality imaging in the selection of heart failure patients who are candidates for CRT with special focus on the assessment of LV mechanical dyssynchrony, LV myocardial scar tissue extent and LV lead position.