<p>Diuretics are a cornerstone of supportive therapy in pediatric patients, widely used for the management of edema, fluid overload, hypertension, and various other kidney diseases. Their clinical utility, however, is strongly influenced by developmental differences in kidney physiology, age-related pharmacokinetics, underlying kidney disease, and the risk of adverse effects unique to children. This review presents an extensive, evidence-informed synthesis of diuretic therapy in pediatric kidney disorders, encompassing pharmacology, mechanisms of action, indications, drug interactions, and safety considerations. We review the role of diuretics across common conditions in pediatric nephrology, including nephrotic syndrome, chronic kidney disease, acute kidney injury, hypertension, hypercalcemia, hypercalciuria, and nephrogenic diabetes insipidus. Special populations, including neonates and adolescents, are discussed, highlighting developmental pharmacology, vulnerability to toxicity, and long-term growth and bone health concerns. The review also summarizes emerging data on newer diuretic therapies, including sodium–glucose cotransporter-2 inhibitors, vasopressin receptor antagonists, and non-steroidal mineralocorticoid receptor antagonists, while emphasizing the current limitations of pediatric evidence. Adverse effects, including electrolyte disturbances, nephrocalcinosis, ototoxicity, and metabolic complications, are systematically addressed with practical monitoring recommendations. Overall, this review underscores that diuretics in children should be used judiciously, individualized to age and kidney function, closely monitored for potential harm, and integrated with definitive disease-modifying therapies to optimize outcomes in pediatric kidney care.</p> Graphical Abstract <p>A higher resolution version of the Graphical abstract is available as <InternalRef RefID="MOESM2">Supplementary information</InternalRef></p> <p></p>