Background: Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children. Methods: Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. AGREE statement was followed to prepare this document. Results: Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C). Conclusions: Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.