Extracorporeal membrane oxygenation (ECMO) is a life-saving technology that temporarily replaces the function of the heart and lungs. It is a supportive modality rather than a therapeutic tool that provides gas exchange and mechanical hemodynamic support for neonates with an acute, reversible respiratory or cardiac condition. This support spares the infant from the deleterious effects of high Fi02, high airway pressure, traumatic mechanical ventilation, and perfusion impairment. ECMO was first used in newborns in 1974. Since then, the Extracorporeal Life Support Organization (ELSO) has recorded approximately 36,000 newborns that have been supported with ECMO for a variety of cardiorespiratory disorders. The most common disorders in the newborn treated with ECMO are meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the neonate (PPHN), congenital diaphragmatic hernia (CDH), sepsis, and cardiac support. Depending on the indication for ECMO, the outcome is varied, but overall, a cumulative survival rate of over 80% has been reported for newborns (reported to the ELSO registry since its inception) treated for respiratory failure.1 This chapter will discuss the selection criteria for ECMO in neonates and the management of these babies while on ECMO. It will then discuss ECMO for use in difficult clinical scenarios, such as CDH, and finally review outcome and follow-up of neonates treated with ECMO.