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Introduction: Currently liver biopsy represents the gold standard to assess severity and fibrosis grade in liver diseases. Since this laborious, costly, and invasive procedure is associated with possible complications, non-invasive methods and biomarkers, which allow for an easy, reliable, and repeatable assessment of liver disease are warranted. Cytokeratin (CK) 18 is an intermediary filament protein, expressed in hepatocytes, which is proteolytically cleaved during liver damage. The resultant CK-18 fragments are released by hepatocytes and can be detected in serum., Methods: A selective literature search in PubMed for original publications about the detection of CK-18 cell death markers in liver diseases was undertaken., Results: Assessment of CK-18 cell death biomarkers allows for the early detection of liver damage in acute and chronic liver diseases. This is even feasible when transaminases are in the normal ranges. Detection of CK-18 biomarkers can also hint at disease activity and severity. For example, patients with non-alcoholic steatohepatitis exhibit elevated serum cell-death markers compared to those with simple steatosis. Furthermore, in patients with relevant fibrosis higher CK-18 values are found as compared to those with low fibrosis. In acute liver failure, cell death biomarkers may assist decision finding for the necessity of liver transplantation., Discussion: Due to promising results of various studies, CK-18 cell death markers could be applied in clinical routine soon., (© Georg Thieme Verlag KG Stuttgart · New York.)