Careful management of fluid and electrolytes has long been an intrinsic part of pediatric practice. However, the augmentation of these manipulations through the rational use of diuretic agents requires considerable skill. In pediatric medicine, the regulation of pharmacokinetic processes and their interface with pharmacodynamic processes show dramatic age-related changes. These ontogenetic processes and their modification by various disease states must be considered carefully before selection and application of diuretic agents. The available data concerning the ontogeny of renal function and the attempts to apply diuretic therapy to pediatric disease are reviewed. It is concluded that results obtained to date suffer from the absence of a rigorous attempt to answer the fundamental therapeutic questions: What drug? What dose? What duration of therapy? A rational "target-effect" strategy is proposed for the application of diuretic agents to pediatric medicine.