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Extracorporeal membrane oxygenation (ECMO) has become a nearly standard treatment for neonates with refractory hypoxemic respiratory failure due to various disease. Even though in the non-neonatal age the experience is less extensive, an increased widespread interest on the possible applications in children with severe life-threatening respiratory or cardiovascular insufficiency is well documented in the literature. General contraindications include presence of active bleeding, underlying lethal disease, congenital malformations, or severe brain damage. Whilst in the neonatal population common entry criteria have been widely accepted, the identification of precise parameters capable to predict mortality and thus indicating an ECMO support in older patients are still lacking. At present, nonetheless, more than 10.000 newborns and 1.000 children with severe respiratory insufficiency at high mortality risk have received an ECMO treatment, with a survival rate of more than 80% and 50%, respectively. The initial results of our ECMO program for both neonatal and pediatric patients with refractory respiratory failure are encouraging, both in terms of mortality and morbidity, and they will be briefly discussed.