The homeostatic liver is characterized by rare cell proliferation and lack of de novo ECM deposition. During regeneration, epithelial replacement occurs predominantly via hepatocyte proliferation and, to a minor degree, through the activation of ductal progenitors. Resident (Kupffer) and bone marrow–recruited macrophages phagocytose the dead epithelium and launch an inflammatory cascade (e.g., TNF-α, IL-6). CXCR7/CXCR4⁺ LSECs provide mitogenic signals (HGF, WNT2) that sustain hepatocyte proliferation. HSCs transdifferentiate into myofibroblasts that deposit ECM on the wound site, although this matrix can be degraded via MMPs. In fibrosis, the hepatocyte compartment is highly senescent and ductal progenitor expansion becomes predominant. Monocyte-derived Ly6C^hi macrophages (secreting TGF-β, thrombospondin 1) and CXCR4⁺ LSECs (secreting TGF-β, BMP2, and PDGFC) collectively enhance myofibroblast proliferation and survival. Myofibroblasts, in turn, secrete high levels of TIMPs, which inhibit MMPs and cause excessive matrix accumulation. A Th1- versus Th2-skewed immune system favors regeneration versus fibrosis, respectively. The resolution of fibrosis entails the return to quiescence/inactivation of myofibroblasts as well as their clearance by NK cells, γδ T cells, and Ly6C^lo macrophages. High levels of MMPs contribute to matrix degradation. The mechanisms of epithelial replacement at this stage have not been fully elucidated.