For more than half a century, metabolic perturbations have been explored in the failing myocardium, highlighting a reversion to a more fetal-like metabolic profile (characterized by depressed fatty acid oxidation and concomitant increased reliance on use of glucose). More recently, alterations in ketone body and amino acid/protein metabolism have been described during heart failure, as well as mitochondrial dysfunction and perturbed metabolic signaling (e.g., acetylation, O-GlcNAcylation). Although numerous mechanisms are likely involved, the current review provides recent advances regarding the metabolic origins of heart failure, and their potential contribution toward contractile dysfunction of the heart.