Acute-on-chronic liver failure (ACLF) is a severe syndrome characterized by acute decompensation due to triggers such as infection or alcohol abuse in patients with chronic liver disease, marked by rapid deterioration of liver function accompanied by multiple organ failure and high short-term mortality. Effective therapeutic options are currently lacking, and liver transplantation remains the only life-saving intervention, which can achieve favorable outcomes in strictly selected patients, although prognosis is influenced by multiple factors. Given the high incidence of ACLF, persistent shortage of donor livers, and expanding indications for liver transplantation, the role of liver transplantation in ACLF remains controversial. This article reviews the etiology, diagnosis, and prognostic models of ACLF, and systematically analyzes the current status of liver transplantation application, predictors of post-transplant mortality, recipient selection, and evidence for optimal timing, aiming to provide references for clinical decision-making.