Left ventricular remodeling is the major mechanism leading to cardiac enlargement, failure, and death after myocardial infarction. It is associated with early disruption of collagen matrix and expansion of the infarct zone (IZ) followed by progressive global ventricular dilation, hypertrophy of the noninfarct zone (NIZ), and further global dysfunction. In parallel, it is associated with healing which repairs the IZ with collagenous scar. Mechanical deformation forces, including ventricular diastolic and systolic loads, mediate structural remodeling during healing, and beyond. Experimental and clinical evidence indicate that early and prolonged impedance reduction and diastolic unloading with nitric oxide donors like nitrates can effectively limit remodeling. Other benefits are mediated by limitation of infarct size and transmurality, improvement of left ventricular hemodynamics and collateral flow, decreased reperfusion injury, and antithrombotic effects. In addition to these benefits, nitrates have nonhemodynamic, antigrowth and cellular actions that limit progressive remodeling after infarction.