Liver fibrosis and in particular cirrhosis have become major endpoints in clinical trials of patients with chronic liver diseases. Here, viral hepatitis, alcoholic and non-alcoholic steatohepatitis have become the major etiologies. We have made great progress in our understanding of the mechanisms and the cell biology of liver fibrosis and have already made the transition from preclinical testing of antifibrotic agents and strategies towards clinical translation. There continues to be an urgent need for specific antifibrotic therapies, despite the advent of highly potent antiviral agents that can even induce regression of advanced fibrosis. This review addresses central mechanisms and cells to be targeted, current antifibrotic drug trials, and the state of non-invasive biomarker development that is key to rapid clinical progress and to a personalized treatment of fibrosis.