End-stage liver disease in children presents a challenging array of medical and psychosocial problems for the health care delivery team. Many of these problems are similar to those encountered by caregivers of adults with end-stage liver disease, such as the development of complications of cirrhosis, including ascites, spontaneous bacterial peritonitis, and esophageal variceal hemorrhage. However, the natural history of disease progression in children and their responses to medical therapy can differ significantly from that of their adult counterparts. Children with end-stage liver disease are especially vulnerable to nutritional compromise; if not effectively managed, this can seriously impact long-term outcomes and survival both before and after liver transplantation. Moreover, close attention must be given to vaccination status and the clinical setting at which health care is delivered to optimize outcomes and the delivery of high-quality pediatric health care. In this review, we address important components of the evaluation and management of children with chronic end-stage liver disease.