Few things in life are more irritating than failing to recognize the obvious. A case in point is energy substrate metabolism as a potential target of pharmacological agents for improving function of the failing heart. The complexities of hemodynamics, coronary flow, and cardiac structure obscure the simple fact that the heart is an efficient converter of energy. The reasoning is straightforward: In a series of highly regulated, enzyme-catalyzed reactions, heart muscle converts chemical energy into mechanical energy. 1 Although metabolism and function in the heart are inextricably linked (Figure), few investigators have considered energy substrate metabolism and the first law of thermodynamics (which states that all energy is conserved) as paradigms for the treatment of heart failure. However, interest in this area is growing.