Significant strides have been made in the medical therapy of chronic CHF in the past two decades. Treatment has evolved from therapy based on the older concepts of the pathophysiology of CHF to evidence-guided therapy supported by results of major landmark studies that expand the understanding of the pathophysiology. Attenuation of neurohumoral activation is now a goal of pharmacological therapy, and we know that agents that offer hemodynamic and early clinical improvement may not necessarily prolong survival-unless they also modulate these neurohormonal systems. Positive inotropic therapy (e.g., use of a digitalis glycoside) is no longer considered essential in patients with CHF in sinus rhythm. Although impressive hemodynamic benefits can be observed with the use of positive inotropic agents, long-term treatment with these drugs has not produced clinical benefits and may increase mortality. Long before the current concerns about the use of positive inotropic therapy for CHF, cardiovascular physiologists had advised that contractility does not equate with overall cardiac performance. Stimulation of myocardial contractility is a property of digoxin therapy. However, cardiac function is governed by four determinants: preload, afterload, rhythm, and contractility. All four require control. Treatment aimed at reducing preload and afterload and improving arrhythmias can achieve cardiac compensation by reducing cardiac work without the need for digoxin therapy or other inotropic drugs.