Extracorporeal membrane oxygenation (ECMO) is an invasive life support technique that requires a blood pump, an artificial membrane lung, and vascular cannulae to drain de-oxygenated blood, remove carbon dioxide, oxygenate, and return it to the patient. ECMO is generally used to provide advanced and prolonged cardiopulmonary support in patients with refractory acute cardiac and/or respiratory failure. After its first use in 1975 to manage a severe form of meconium aspiration syndrome with resultant pulmonary hypertension, the following years were dominated by the use of ECMO to manage neonatal respiratory failure and limited to a few centers across the world. In the 1990s, evidence for neonatal respiratory ECMO support increased; however, the number of cases began to decline with the use of newer pharmacologic therapies (e.g., inhaled nitric oxide, exogenous surfactant, and high-frequency oscillatory ventilation). On the contrary, pediatric ECMO sustained steady growth. Combined advances in ECMO technology and bedside medical management have improved general outcomes, although ECMO-related complications remain challenging. Point-of-care ultrasound (POCUS) is an essential tool to monitor all phases of neonatal and pediatric ECMO: evaluation of ECMO candidacy, ultrasound-guided ECMO cannulation, daily evaluation of heart and lung function and brain perfusion, detection and management of major complications, and weaning from ECMO support. Conclusion: Based on these considerations and on the lack of specific guidelines for the use of POCUS in the neonatal and pediatric ECMO setting, the aim of this paper is to provide a systematic overview for the application of POCUS during ECMO support in these populations.