The diagnostic work-up of patients with liver diseases includes taking a past history, a physical examination, incl. an abdominal ultrasound examination or a duplex ultrasonography, general laboratory analyses, etiology-defining analyses, imaging studies and in special situations a percutaneous or transjugular liver biopsy or a laparoscopy. Following this algorithm it is possible to identify in most cases the etiology of the liver disease. The exact diagnosis is key for the understanding of the natural course and prognosis of the liver disease and for the indication for therapy, the choice of the optimal therapeutic strategy and the assessment of its response. Of particular importance is at the time of the first diagnosis of a liver disease to exclude or identify coexisting etiologies, e. g., alcohol use and HCV infection.