Left ventricular (LV) remodeling describes dynamic changes in ventricular size and shape that result from hemodynamic and metabolic insults to the failing heart. The remodeling hypothesis in heart failure asserts that LV remodeling is the central pathophysiologic lesion whereby alterations in cardiac structure are followed by impairment in function, with a wide range of genetic-environment interactions that determine the ultimate phenotype. Several therapeutic targets of LV remodeling have already been exploited (such as neurohormonal and cytokine activation). On the other hand, great efforts are still being made to understand the complex array of genetic and metabolic derangements. Nevertheless, we have realized that there is no single phenotypic change, protein expression, or signal-transduction pathway that is dominant in the process of cardiac remodeling. This implies that better characterization of this heterogeneous heart failure phenotype is desperately needed.