Acute-on-chronic liver failure (ACLF) is a severe liver disease with high mortality in China. Early diagnosis could reduce complications and improve the survival rate. In the present review, the definition, etiology, and pathogenesis related to inflammatory response, reactive oxygen species, and metabolism are reviewed. Also, the new approaches to the treatment of ACLF and prognostic factors are summarized. Generally, the development of ACLF is considered to be life-threatening for patients. Therefore, a universal definition of ACLF should be proposed, which would provide good guidance and standard for the clinical diagnosis and treatment of ACLF in China. In addition, the risk factors for ACLF in patients with chronic liver diseases need to be determined by prospective studies.