Extracorporeal membrane oxygenation was first successfully achieved in 1975 in a neonate with meconium aspiration. Neonatal extracorporeal membrane oxygenation has expanded to include hemodynamic support in cardiovascular collapse before and after cardiac surgery, medical heart disease, and rescue therapy for cardiac arrest. Advances in pump technology, circuit biocompatibility, and oxygenators efficiency have allowed extracorporeal membrane oxygenation to support neonates with increasingly complex pathophysiology. Contraindications include extreme prematurity, extremely low birth weight, lethal chromosomal abnormalities, uncontrollable hemorrhage, uncontrollable disseminated intravascular coagulopathy, and severe irreversible brain injury. The future will involve collaboration to guide and evolve evidence-based practices for this life-sustaining therapy.