The human/animal heart, comprised of cells called "myocytes" is an incredible organ that to remain beating must be fueled constantly via the hydrolysis of adenosine tri-phosphate (ATP). Deriving most of its ATP from mitochondrial oxidative phosphorylation (ox phos), and a smaller amount from "glycolysis", i.e., glucose conversion to pyruvate or lactate, the heart helps in the delivery of oxygen (via hemoglobin) to every organ/tissue in our body. Then, the empty (deoxy) hemoglobin returns to load more oxygen and the journey to tissues is repeated 24 h a day, year after year, until "death do us part". To support this essential "pumping" process the heart must work constantly, i.e., 70-80 years (life expectancy in the U.S.). This is a remarkable feat when compared with one of our most costly people-made technologies, i.e., automobiles (cars). In the past century, it was rare to see the family car survive more than 10-15 years unless it had been subjected to motor replacement surgery. Most were laid to rest at a much earlier age. Now, in this new millennium should a brilliant car manufacturer succeed in constructing a car engine as efficient as the human heart, each family member requiring a car would need only one per life time. With this in mind, one of the major future "matters of the heart" is to keep it pumping, not only for the current 70-80 year life span but much longer. To do this depends on, among other matters, the two processes noted above, i.e., oxidative phosphorylation and glycolysis. The former is strictly a mitochondrial process that works only in the presence of oxygen whereas glycolysis, dependent on mitochondrial bound hexokinase 2 (MB-HK-2), works either in the presence or absence of oxygen. In addition, the MB-HK 2 is anti-apoptotic and helps with other factors to retard cell death. Current estimates reveal that the human heart of an individual living 70-80 years will have undergone 2.5-3.0 billion beats, a feat that is energetically feasible only due to the heart cells' (cardiomyocytes) large population of mitochondria with bound HK-2.