The incidence and prevalence of heart failure is on the rise. It has become the single most expensive health care item in the United States and the number one discharge diagnosis in the elderly. The goals of therapy include both prevention and treatment of heart failure. In recent years research studies and randomized clinical trials have revolutionized the understanding of the pathophysiology and treatment of this disease. This article focuses on the medical management of chronic systolic heart failure based on the pathophysiology of the disease. Systolic heart failure is characterized by a decrease in left ventricular function and cardiac output, which results in activation of several neurohormonal compensatory systems. The long term effects of this neurohormonal activation leads to further deterioration of cardiac function. The use of hydralazine and nitrates to reduce the systemic vascular resistance was the first to show an improvement in mortality and morbidity. Then angiotensin converting enzyme inhibitors, by inhibiting the renin angiotensin system, demonstrated a greater improvement in mortality and morbidity. More recently the inhibition of the sympathetic stimulation with beta-blockers has been shown to have an additive effect on morbidity and mortality in combination with angiotensin-converting enzyme inhibitors. Digoxin and diuretics remain important for improving symptoms and decreasing hospitalizations but have not been shown to decrease mortality. The most recent advance in the treatment of cardiac failure is the demonstration that the aldosterone antagonists, spironolactone decreases morbidity and mortality.