In most patients with heart failure, an imbalance between energy production and energy utilization leads to a state of chronic energy starvation. This imbalance is due both to increased energy demands caused by overloading of myocardial cells in the failing heart, and to a decreased energy supply caused by reduced perfusion, altered cell architecture, and molecular changes in the hypertrophied heart. Energy starvation has important therapeutic implications in the failing heart. Because the systems that relax the heart are especially sensitive to energetic state, inotropic agents could exacerbate relaxation abnormalities and promote arrhythmias. More important is the likelihood that inotropic agents, which increase cardiac energy expenditure, accelerate cell damage and so worsen prognosis in this condition. Vasodilators and negative inotropic agents, on the other hand, by decreasing energy utilization should improve the balance between energy delivery and energy expenditure in the failing heart.