Acute on chronic liver failure (ACLF) is an inflammation-based disorder that occurs in patients with underlying liver disease and is characterized by hepatic and extrahepatic organ failure. Morbidity and mortality are high in patients with ACLF, and therefore prevention and early identification are critical to improve outcome. The purpose of this article is to define ACLF, describe ways to identify the expected outcome of ACLF after development, and illustrate interventions to prevent it and when it is not preventable reduce associated morbidity and mortality.