Liver support systems aim to provide temporary support of liver function while maintaining extra-hepatic function in patients with liver failure. Important advances have been achieved in the design of artificial and bio-artificial devices, but the current systems are far from meeting the ideal. Artificial devices provide detoxification through different dialysis procedures, whereas bio-artificial devices add synthetic functions by incorporating a cellular component into the system. Overall, liver support systems have consistently shown beneficial effects on the pathophysiology of liver failure, especially in acute-on-chronic liver failure. However, these beneficial effects have not been translated into an improvement of survival. Our review discusses the current evidence, paying special attention to the clinical aspects of (bio)-artificial liver support devices.