Heart failure is one of the leading causes of death worldwide and has been singled out as an emerging epidemic. 1, 2 With a 5-year survival rate of 50%, heart failure poses a tremendous burden on our economic and healthcare system. Despite extensive interests and paramount clinical needs, our understanding of heart failure remains incomplete. As a consequence, there is currently no cure. Hypertension is one of the most important risk factors of heart failure. Under high blood pressure, cardiac ventricular wall stress is mounted. According to LaplaceLs law, an increase in cardiac wall thickness can effectively ameliorate wall stress. 3 This so-called concentric cardiac growth is achieved by upregulation of sarcomere biosynthesis and enlargement of individual cardiac myocytes attributed to limited replicative capacity in the adult heart. In response to persistent stress, however, this once adaptive hypertrophic growth may progress into decompensation and heart failure. Over the past few decades, numerous signaling molecules and pathways have been identified in cardiac hypertrophic growth and heart failure. 4 These processes involve extensive cardiac remodeling in metabolism, structure, and electrophysiology. Growing evidence indicates that metabolic remodeling precedes most, if not all, other pathological alterations and likely plays an essential role in cardiac hypertrophy and heart failure. 5–10 Ischemic heart disease is another critical contributing factor to heart failure. Patients surviving myocardial infarction (MI) may undergo extensive pathological remodeling in the heart with major metabolic derangements. Here, we review recent findings of cardiac metabolic changes in response to hemodynamic stress and cardiac ischemia with a focus on glucose utilization. We also discuss potential therapeutic targets from carbohydrate metabolic pathways to tackle this devastating heart disease.