A severe burn injury induces a hypermetabolic response that negatively impacts glucose homeostasis, fat metabolism, and protein balance. The liver plays a pivotal role mediating the disarrangements observed in glycogenolysis, glycolysis, gluconeogenesis, lipolysis, and proteolysis, all of which are part of this systemic response. Clinical observations and investigative studies have helped us to understand the function of the liver in the pathophysiology of severe burn injuries including the association between preserved hepatic function and favorable outcomes. This chapter summarizes the key concepts, underlying biologic mechanisms, and the latest advances addressing the post-burn role of the liver.