In this issue of Clinics in Liver Disease, guest editor Dr. Nikolaos T. Pyrsopoulos brings his considerable expertise to the topic of Acute-on-Chronic Liver Failure. Recent studies indicate that as many as one in four patients with cirrhosis develop acute-on-chronic liver failure (ACLF) and 25% die within one month. This issue, the first devoted to this topic, provides thorough coverage of critical clinical interventions, including diagnosis, treatment, and management. It also focuses on early recognition of ACLF, which is important for the initiation of aggressive management and ultimately, saving lives. Contains 17 practice-oriented topics including ACLF: mechanisms of disease and multisystemic involvement; the clinical spectrum and manifestations of ACLF; management of ACLF; maximizing the donor potential for patients with ACLF Listed for Liver Transplant; future approaches and therapeutic modalities for ACLF; and more.  Provides in-depth clinical reviews of acute-on-chronic liver failure, offering actionable insights for clinical practice.  Presents the latest information on this timely, focused topic under the leadership of experienced editors in the field. Authors synthesize and distill the latest research and practice guidelines to create clinically significant, topic-based reviews.