<p>Over the past decade, advances in neonatal nephrology have expanded the ability to provide kidney replacement therapy to increasingly smaller and more medically complex infants. The development and adaptation of devices designed specifically for infants have facilitated safer delivery of continuous kidney replacement therapy (CKRT), with reduced extracorporeal circuit volumes, smaller filters, lower blood flow requirements, and improved precision of fluid balance. As a result, CKRT use in critically ill neonates continues to increase. Indications for neonatal CKRT include acute kidney injury and fluid overload, as in older children and adults, but also extend to congenital kidney failure and inborn errors of metabolism. The neonatal population presents unique challenges related to vascular access and the need to provide adequate nutrition to support growth. A thorough understanding of solute clearance mechanisms, dosing strategies, device selection, anticoagulation options, and complication management is essential to optimize outcomes. This case-based educational review summarizes current principles, technologies, and available evidence guiding neonatal CKRT practice, with special considerations for neonates receiving prolonged course of CKRT for kidney failure.</p> Graphical Abstract <p>A higher resolution version of the Graphical abstract is available as <InternalRef RefID="MOESM1">Supplementary information</InternalRef>.</p> <p></p>