Acute-on-chronic liver failure (ACLF) is a type of severe clinical syndrome which occurs on the basis of chronic liver diseases and has the main clinical features of acute liver decompensation, extrahepatic organ damage, and high short-term mortality rate. The underlying diseases of chronic liver diseases are mainly alcoholic hepatitis and chronic hepatitis C in Western countries, while chronic hepatitis B is the main underlying disease of chronic liver diseases in China and the Asia-Pacific region. Although there are differences in underlying liver diseases between the East and the West, the common pathological basis of most ACLF patients is usually liver fibrosis or cirrhosis caused by long-term chronic liver injury. At present, the research on ACLF has been widely carried out all over the world; however, due to the differences in region, population, and disease triggers, no consensus has been reached on the definition, diagnostic criteria, and disease management of ACLF between the East and the West. This article elaborates on the definition, pathogenesis, and management of ACLF, in order to provide clinicians with new therapeutic strategies that would improve the prognosis of ACLF.