Since publication of the first descriptions of acute liver failure (ALF) as a distinct clinical entity in the 1950's, the understanding of the pathophysiologic mechanisms involved and the management options have increased substantially. ALF still represents a major challenge for todays hepatologists, because it can rapidly lead to multiorgan failure and death that may be preventable with appropriate intervention. This article summarizes the basic patho-physiology underlying ALF, compares epidemiologic trends in the United States, the United Kingdom, and the Far East, and reviews prognostic markers and treatment options for ALF.