The medical treatment of heart failure has evolved over the past 40 years, from the primary use of diuretics and digitalis in the 1960s to the use of inotropic agents and vasodilators in the 1970s. More recently, the focus has been on the neurohormonal system, specifically the renin-angiotensin-aldosterone system and the sympathetic nervous system. Drugs that inhibit or block these systems (eg, angiotensin-converting enzyme inhibitors and β-blocking drugs) are the primary agents recommended in recent heart failure guidelines. However, the actual percent reduction in mortality associated with the use of these agents has been relatively modest. This article will review the results and limitations of medical therapy for heart failure. Our understanding of the pathogenesis of heart failure may be incomplete, and alternative strategies, including mechanical devices, may play an increasing role in the treatment of heart failure in the future.