This review briefly highlights the major mechanisms of left ventricular (LV) remodeling following myocardial infarction in heart failure and presents novel strategies to limit infarct size and retard the progression of LV remodeling. This is important since interventions that have been shown to improve mortality in patients with heart failure such as angiotensin converting enzyme inhibitor and beta-blockers had a favorable impact on the LV remodeling process. Although several other animal models of heart failure are available, we chose the rat infarct model because of its accurate reflection of human pathophysiology. It is clear from this review that the understanding of the mechanisms responsible for the regression of ventricular remodeling is still unclear. Further investigations in this area will certainly lead to the development of new therapy for heart failure.