Major events involved in the fibrogenic progression of chronic liver diseases. CLDs may involve different aetiological agents or conditions able to cause persisting (i.e., chronic) parenchymal liver injury and then hepatocyte cell death (either necrosis or apoptosis). As a result of chronic liver injury, a persistent inflammatory reaction can occur which may significantly affect the progression of the disease by either contributing to the perpetuation of parenchymal injury or by generating a microenvironment pressure in terms of growth factor, cytokine and other mediators that can efficiently favour tissue repair and the activation of pro-fibrogenic cells. This is the scenario that will lead to the persistent activation of myofibroblast-like cells from different precursors. Activated MFs will contribute either to perpetuation of inflammation by releasing pro-inflammatory mediators or to the excess synthesis and accumulation of fibrillar (rich in collagen type I and III) extracellular matrix (ECM) components. If the aetiological agent or causal condition persists, the CLD can undergo a fibrosclerotic progression to cirrhosis and liver failure. Since cirrhosis is characterized by formation of regenerative nodules of parenchyma surrounded and separated by fibrotic septa, this scenario is intrinsically associated with significant changes in hepatic angio-architecture. Fibrosis itself as well as the development of hypoxic areas have been reported to further contribute to perpetuation of liver injury.