Liver regeneration is a complex, highly orchestrated process that restores hepatic mass and function after injury or resection. It relies primarily on proliferation and hypertrophy of mature hepatocytes, with facultative contributions from biliary epithelial cells and progenitor pathways when hepatocyte replication is impaired. Non-parenchymal cells—Kupffer cells, hepatic stellate cells, and liver sinusoidal endothelial cells—coordinate immune responses, extracellular matrix remodeling, angiogenesis, and metabolic adaptation. Cytokines (IL-6, TNF-α) and growth factors (HGF, EGF, TGF-α) initiate hepatocyte priming, while signaling networks (Wnt/β-catenin, Notch, Hippo/YAP) integrate vascular, metabolic, and inflammatory cues to drive proliferation and terminate growth once the liver-to-body size ratio is restored. Microenvironmental factors, oxygenation, nutrient supply, and gut–liver interactions critically influence outcomes. Following partial hepatectomy, regeneration follows a predictable timeline from rapid cytokine release to proliferative expansion and remodeling, monitored by laboratory and imaging parameters. Post-hepatectomy liver failure arises from inadequate remnant volume or quality, ischemia–reperfusion injury, infection, or immune-fibrotic imbalance. Understanding these mechanisms supports surgical strategies that maximize regenerative potential and improve patient outcomes.