Acute liver failure (ALF) is a rare but life-threatening clinical syndrome with a broad range of causes. Significant improvements in outcome have occurred over the last 50 years, resulting not only from incremental improvements in specialist critical care and a step-change following the introduction of transplantation for this indication, but also better and more effective treatment started early at the site of first presentation.1 2 Emergency liver transplantation (LTx) remains an important intervention and the decision regarding the need for LTx remains key to management, though non-transplant therapies now appear effective for many causes of the condition. In this short review, we will outline issues in the recognition and management of ALF and ongoing challenges in its treatment.