Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD may cause liver fibrosis and proceed to cirrhosis that eventually leads to hepatocellular carcinoma. The diagnosis is based on anamnesis (exclusion of extensive alcohol ingestion), clinical symptoms, imaging techniques, and liver biopsy, which is still the gold standard though associated with complications and sampling errors. As a non-invasive method, the use of serological biomarkers seems to be a good opportunity to gain a simple and reproducible assessment of ongoing liver injury. Cytokeratin-18 (CK-18) is an intermediate filament protein which is secreted during hepatic injury and detectable in patients’ sera. Recent data indicate that CK-18 levels may differentiate between simple steatosis and non-alcoholic steatohepatitis (NASH). Adiponectin is produced in adipocytes has antiapoptotic features in hepatocytes. Adiponectin production depends on adipocytes size. Furthermore the additional determination of CK-18 and adiponectin allows conclusions about the type and severity of liver disease and can potentially contribute to clinical diagnosis and management in clinical practice.