It has become common sense that the failing heart is an "engine out of fuel". However, undisputable evidence that, indeed, the failing heart is limited by insufficient ATP supply is currently lacking. Over the last couple of years, an increasingly complex picture of mechanisms evolved that suggests that potentially metabolic intermediates and redox state could play the more dominant roles for signaling that eventually results in left ventricular remodeling and contractile dysfunction. In the pathophysiology of heart failure, mitochondria emerge in the crossfire of defective excitation-contraction coupling and increased energetic demand, which may provoke oxidative stress as an important upstream mediator of cardiac remodeling and cell death. Thus, future therapies may be guided towards restoring defective ion homeostasis and mitochondrial redox shifts rather than aiming solely at improving the generation of ATP.