Liver fibrosis and the mechanisms of its progression are topics as old as hepatology itself. Three aspects of liver fibrosis are covered in this issue: cofactors of liver disease progression, noninvasive methods to assess the stage of liver fibrosis, and current and future pharmacolocigal approaches to treat liver fibrosis. In chronic hepatitis B and C, liver disease progression is highly variable both among patients and over time, with some individuals running a benign clinical course for decades and others rapidly and dramatically progressing to end-stage liver disease within a few years. These different outcomes are mostly due to the variable impact of environmental and host cofactors, such as alcohol intake, diabetes and metabolic syndrome, tobacco and cannabis use. The identification and management of these cofactors are essential, because in many cases they may reduce the rate of response to antiviral therapy. Among the above-mentioned cofactors, a key role is currently played by metabolic syndrome; thus, proper appreciation of its consequences on liver disease progression is of paramount importance. The gold standard for assessing the stages of liver fibrosis remains the liver biopsy. However, several noninvasive methods for staging liver fibrosis have been introduced into clinical practice: they are not only safe and more acceptable to physicians and patients, but they also allow the monitoring of liver disease progression at a higher frequency than is permitted for liver biopsy. Simple scoring systems for liver disease progression have been available for a long time, and more recent algorithms have sparked a major debate, culminating in sometimes complex decisional trees. The pharmacological treatment of fibrosis relies essentially on stopping the underlying liver disease via the elimination of its etiological factor (such as using antivirals in hepatitis B and C or withdrawing alcohol in alcohol hepatitis). However, the goal of limiting – and possibly reverting – the fibrogenic process can be approached in a variety of ways, all directly targeting the mediators involved. Albeit mostly at the preclinical stage, many antifibrotic drugs are likely to reach the clinical practice within a few years, adding to the effective armamentarium of hepatologists.