This review deals with studies carried out to investigate changes in mitochondrial bioenergetic aspects and membrane functionality during the regenerative process that occurs in liver after partial resection (70%). Studies aimed at investigating changes in hepatocyte and mitochondria ultrastructure within the hepatic acinus during liver regeneration are also reported. In addition, the effect of thyroid state on the regenerative process will be considered. Partial hepatectomy induces cell proliferation until the original mass of the liver is restored. During the prereplicative phase of liver regeneration, drastic changes in the metabolism of the remaining liver occur, including impairment of mitochondrial bioenergetics and changes in the inner mitochondrial membrane permeability properties. Significant changes in the ultrastructure of hepatocytes and mitochondria in situ also occur, and a preferential zonation of altered mitochondria in periportal hepatocytes, the cells that exhibit major structural attributes to proliferate, is observed. Thyroid hormone serum levels influence the biochemical properties and the membrane functionality of mitochondria during liver regeneration. The involvement of mitochondria- mediated signaling in the modulation of the liver regenerative process is discussed.