Liver regeneration following hepatic resection is closely linked to metabolic adaptations that balance the energy demands of regeneration with homeostasis and liver function. This process involves metabolic remodeling of glucose, lipid, and amino acid metabolism, including systemic substrate mobilization to support regeneration and cell proliferation at multiple levels. Metabolic liver diseases can impair regeneration, whereas therapeutic interventions may enhance it. This chapter briefly explores the metabolic alterations that occur during liver regeneration.