The most common cause of heart failure is ischemic heart disease. There is strong evidence, however, that the ischemic insult is only part of a cascade of events that lead to the progressive failing of the heart’s ability to pump. It is the understanding of this cascade of events that has changed the paradigm of the pathophysiology of heart failure. Heart failure was once thought to be primarily a volume disorder, treated only with rotating tourniquets and diuretics. More recently, left ventricular systolic dysfunction was conceptualized in terms of hemodynamic parameters such as ejection fraction and afterload. The goals of treatment were to increase contractility and to decrease afterload. While concerns about fluid status and hemodynamic parameters are still valid under the new paradigm, interventions targeted to these issues alone provide primarily symptomatic relief and have little impact on mortality.