Establishing the aetiology of acute hepatic failure is essential for correct and timely management. An exhaustive history and examination is crucial in targeting investigations and initiating management. Clinical assessment allows risk stratification, identifying those patients who can be managed locally from those best served in a specialist centre with liver transplantation capability. History should focus on the presenting problem, time of onset and speed of deterioration, and establish features consistent with hyperacute, acute or subacute ALF to guide prognostication. Examination should initially focus on rapid assessment and resuscitation before searching for signs leading to more specific differential diagnoses. Investigations should encompass the variety of potential causes, ranging from basic to more specialist studies. Prognostication is critical for stratification of those patients who may benefit from a potentially life-saving transplantation. Several risk stratification and predictive tools exist to differentiate those patients likely to recover, those unlikely to survive despite maximal intervention, and those who would potentially benefit from transplantation.