We critically examined research on health-related quality of life (HRQL) in children and adolescents after liver transplantation. The specific aims were to identify research studies on HRQL after liver transplantation, to critique the methodological quality of the studies, to estimate overall HRQL after transplant, and to make recommendations for future research. Databases searched included Medline, Cumulative Index to Nursing and the Allied Health Literature, PsycINFO, EMBASE, Allied and Complementary Medicine, Institute for Scientific Information Web of Science, and Applied Social Sciences Index and Abstracts. Searches also were made on related Web sites and proceedings of transplantation and associated conferences. Eligible studies involved children between birth and 18 years of age who received isolated orthotopic, auxiliary, or living related liver transplantation. HRQL was assessed through 2 or more of the domains of physical health, psychological functioning, social functioning, family functioning, or general well-being. Eligible studies were abstracted, assessed for methodological quality, and synthesized using the sign test to provide an indication of the effect of liver transplantation on each HRQL domain. The synthesis of findings suggested an improvement in HRQL in comparison with pretransplant status; there was a trend toward a worse HRQL in comparison with the healthy population and better than those with other chronic illnesses. In conclusion, liver transplantation in childhood has a negative impact on some aspects of HRQL. However, this finding is tentative because of the small number of studies and variable study quality found.