OBJECTIVE: To provide a comprehensive evidence-based review of extracorporeal membrane oxygenation for neonatal and pediatric respiratory failure. DATA SOURCE: A thorough computerized bibliographic search of the clinical literature regarding the use of extracorporeal membrane oxygenation in the neonatal and pediatric populations. STUDY SELECTION: Clinical trials published between January 1, 2002, and October 1, 2012, including "extracorporeal membrane oxygenation" or "ECMO" and limited to studies involving humans aged 0-18 years. Trials focused on extracorporeal membrane oxygenation for cardiac indications were excluded from this study, unless the study was evaluating ancillary therapies in conjunction with extracorporeal membrane oxygenation. DATA EXTRACTION: Studies were evaluated for inclusion based on reporting of patient outcomes and/or strategic considerations, such as cannulation strategies, timing of extracorporeal membrane oxygenation utilization, and ancillary therapies. DATA SYNTHESIS: Pertinent data are summarized, and the available data are objectively classified based on the value of the study design from which the data are obtained. CONCLUSIONS: Despite a large number of published extracorporeal membrane oxygenation studies, there remains a paucity of high-quality clinical trials. The available data support continued use of extracorporeal membrane oxygenation for respiratory failure refractory to conventional therapy for neonatal and pediatric patients without significant comorbidities. Further research is needed to better quantify the benefit of extracorporeal membrane oxygenation and the utility of many therapies commonly applied to extracorporeal membrane oxygenation patients.