Myocardial failure has been considered to be an irreversible and progressive process characterized by ventricular enlargement, chamber geometric alterations, and diminished pump performance. However, more recent evidence has suggested that certain types of medical therapy may lead to retardation and even reversal of the cardiomyopathic process. In the failing heart, long-term neurohormonal/autocrine-paracrine activation results in abnormalities in myocyte growth, energy production and utilization, calcium flux, and receptor regulation that produce a progressively dysfunctional, mechanically inefficient heart. Interventions such as ACE inhibition and β-blockade result in a reduction in the harmful long-term consequences of neurohormonal/autocrine-paracrine effects and retard the progression of left ventricular dysfunction or ventricular remodeling. Furthermore, in subjects with idiopathic dilated or ischemic cardiomyopathy, antiadrenergic therapy with β-blocking agents appears to be able to partially reverse systolic dysfunction and ventricular remodeling. Although the precise mechanisms underlying this latter effect have not yet been elucidated, the general mechanism appears to be via improvement in the biological function of the cardiac myocyte. Such an improvement in the intrinsic defect(s) responsible for myocardial failure will likely translate into important clinical benefits.