Liver fibrosis and its end-stage, cirrhosis is a growing health burden worldwide. Liver fibrosis is the common wound healing response associated with chronic liver injury. In recent years, there have been major advances in our understanding of the mechanisms underlying fibrosis progression, and how coordinated interactions between parenchymal and non-parenchymal cells impact on the fibrogenic process. However, efficient therapy is still pending. This review by Lotersztajn/Gilgenkrantz team approaches the issue of how targeting cell-intrinsic metabolism impact on fibrosis progression from the angle view of each cell type (hepatic stellate cell, Kupffer cell, hepatocyte or endothelial cell) in order to better define new antifibrotic therapeutic options.