In the last two decades, a new concept of acute-on-chronic liver failure (ALCF) has emerged as a distinctive condition compared to decompensated cirrhosis. ACLF is associated with excessive systemic inflammatory response in patients with underlying chronic liver disease, leading to acute deterioration of liver function, multi-organ failure, as well as high 28-days mortality. Several definitions have been used in adults, but it is also important to recognize in pediatric population and apply dynamic scores, such as AARC-ACLF and CLIF-SOFA Pediatric on admission and at day 3–7 after admission, in order to evaluate prognosis and mortality. Treatment paradigms rely on supportive treatment with early recognition, intensive care unit admission, and prompt evaluation for liver transplant.