The process of left ventricular (LV) remodeling has been shown to be an important predictor of morbidity and mortality in patients with heart failure. Therefore, identifying the cascade of molecular and cellular events that contribute to LV remodeling is likely to provide new and novel targets for preventing disease progression in heart failure. In this issue of Circulation, Li and colleagues1 report that changes in the relative abundance of tissue inhibitors of the metalloproteinases (TIMPs) occur with the development of end-stage human heart failure, thus raising the important possibility that alterations in the extracellular matrix of the failing heart may contribute to disease progression in heart failure. The purpose of this editorial was to place the findings of the study by Li et al, as well as those of recently published reports, in perspective with what we know about myocardial extracellular remodeling in heart failure.