Disturbances of some partial liver functions, such as synthesis, excretion, or biotransformation of xenobiotics, are important for prognosis and ultimate survival in patients presenting with multiple organ dysfunction on the intesive care unit (ICU). The incidence of liver dysfunction is underestimated when traditional "static" measures such as serum-transaminases or bilirubin as opposed to "dynamic" tests, such as clearance tests, are used to diagnose liver dysfunction. Similar to the central role of the failing liver in MODS, extrahepatic complications, such as hepatorenal syndrome and brain edema develop in acute or fulminant hepatic failure and determine the prognosis of the patient. This is reflected in the required presence of hepatic encephalopathy in addition to hyperbilirubinemia and coagulopathy for the diagnosis of acute liver failure. In addition to these clinical signs, dynamic tests, such as indocyanine green clearance, which is available at the bed-side, are useful for the monitoring of perfusion and global liver function. In addition to specific and causal therapeutic interventions, e.g. N-acetylcysteine for paracetamol poisoning or termination of pregnancy for the HELLP-syndrome, new therapeutic measures, e.g. terlipressin/albumin or albumin dialysis are likely to improve the poor prognosis of acute-on-chronic liver failure. Nevertheless, liver transplantation remains the treatment of choice for fulminant hepatic failure when the expected survival is <20%.