Heart failure may be viewed as a progressive disorder that is impelled, at least in part, by progressive left ventricular (LV) remodeling. In the present discussion we will review the role of LV remodeling in the pathogenesis of heart failure, with a focus on the contribution that increased wall stress plays in the development and progression of LV remodeling. The clinical implication of this review is that existing neurohormonal strategies may not completely prevent disease progression in the failing heart, and that adjunctive strategies that are designed to specifically prevent or attenuate LV remodeling may play an important role in the clinical treatment of heart failure.