The liver is a key metabolic organ and governs body energy metabolism. It acts as a hub to metabolically connect various tissues, including skeletal muscle and adipose tissue. The liver stores releases, and recycles potential energy. The strong response from the liver complies with the accelerated metabolic demands of the working muscle. Prolonged acute exercise reduces hepatic blood flow, stimulating hepatic glycogenolysis and gluconeogenesis; but, lipid metabolism shows little change. The main triggers are humoral, but hepatic afferent nerves, cytokines, reactive oxygen species, and changes in hepatic blood flow may all play some role. Regular aerobic exercise training improves blood glucose control during exercise by increasing glycogen stores and up-regulating enzymes involved in gluconeogenesis and carbohydrate metabolism. Lipogenic enzymes are down-regulated, and lipid metabolism is augmented.