Dramatic maturational changes occur in cardiac energy metabolism during cardiac development, differentiation, and postnatal growth. These changes in energy metabolism have important impacts on the ability of the cardiomyocyte to proliferate during early cardiac development, as well as when cardiomyocytes terminally differentiate during later development. During early cardiac development, glycolysis is a major source of energy for proliferating cardiomyocytes. As cardiomyocytes mature and become terminally differentiated, mitochondrial oxidative capacity increases, with fatty acid beta-oxidation becoming a major source of energy for the heart. The increase in mitochondrial oxidative capacity seems to coincide with a decrease in the proliferative ability of the cardiomyocyte. The switch from glycolysis to mitochondrial oxidative metabolism during cardiac development includes both alterations in the transcriptional control and acute alterations in the control of each pathway. Interestingly, if a hypertrophic stress is placed on the adult heart, cardiac energy metabolism switches to a more fetal phenotype, which includes an increase in glycolysis and decrease in mitochondrial fatty acid beta-oxidation. In this article, we review the impact of alterations in energy substrate metabolism on cardiomyocyte proliferation, differentiation, and postnatal maturation.