Acute liver failure remains a condition with substantial mortality in spite of the best available medical care. Liver transplantation is often not possible or delayed, and liver support systems can be used to maintain the patient during the crisis by bridging to transplantation or allowing recovery of the native liver. Bioartificial devices, using porcine or human hepatocytes, have yielded encouraging results on consciousness levels in a number of studies and have generally been found to be safe, although in one large controlled trial reported to date, benefit was restricted to certain subgroups. Artificial devices, like those based on albumin dialysis, are undoubtedly effective in removing protein-bound toxins, and uncontrolled evidence shows some survival benefit. The large multicenter controlled trials necessary for proving the value of these systems are difficult to design. They have to take into account the influence of transplantation, etiology, and other factors on outcome. Achieving a standard medical regime for these critically ill patients between different centers is also difficult.