Cardiac remodeling constitutes a risk factor in cardiovascular disease. It may occur in a variety of circumstances. In hypertension and following myocardial infarction, pharmacological intervention in the remodeling process has been the subject of several studies. But the mechanisms of action of drugs that do contribute to regression of the remodeling response are still a matter of debate. Much of the confusion around the subject comes from the fact that classic arteriolar vasodilators do not result in such regression in hypertensive cardiac hypertrophy. This paper reviews some of the literature to examine whether there is indeed an exceptional position for vasodilators in hypertensive heart disease. Although, conceptually, arteriolar dilatation, and thus afterload reduction, might also have favorable effects on the remodeling response following myocardial infarction, clinical studies suggest the opposite. In the present paper, possible mechanisms are discussed, and evidence is presented that shows that hydralazine has an unexpected effect on the remodeling response at the level of the extracellular matrix.