AbstractThe liver is innervated by both the sympathetic and the parasympathetic nerve systems. These nerves are derived from the splanchnic and vagal nerves that surround the portal vein, hepatic artery, and bile duct. The afferent fiber delivers information regarding osmolality, glucose level, and lipid level in the portal vein to the central nervous system (CNS). In contrast, the efferent fiber is crucial in the regulation of metabolism, blood flow, and bile secretion. Furthermore, liver innervation has been associated with hepatic fibrosis, regeneration, and circadian rhythm. Knowledge of these mechanisms can be applied for potential liver disease treatment.