Lung transplantation can offer improved quality of life and prolonged survival to children who have end-stage cardiopulmonary disease, even in the presence of characteristics that have been considered poor prognostic indicators. At present, children who have pulmonary hypertension tend to be referred for transplantation late in the course of their disease; as a result, almost half die before organs become available. Cardiac catheterization for accurate disease staging, appropriate timing of evaluation and listing for transplantation, and referral to centers experienced in the treatment of children who have end-stage cardiovascular disease are all essential components of a process that will improve survival in such children. Our experience indicates that there may be important developmental differences in the body's response to lung transplantation; thus, protocols that are suitable for older adolescents and adults may be unsuitable for young children. An integrative approach to investigation of these issues, i.e., one in which careful clinical observation and data acquisition are combined with targeted bench research, is most likely to result in insights that will directly benefit patients.