Diuretics are the mainstay of traditional therapy for congestive heart failure. The syndrome of heart failure is now understood to involve complex interactions of neurohumoral substances released in response to poor cardiac function. Developmental changes during infancy and childhood will affect both the activation of systemic neurohumoral responses and the pharmacokinetic and pharmacodynamic actions of diuretics. Few human studies directly evaluate the efficacy of diuretic therapy in heart failure in adults. The pharmacodevelopmental aspects of diuretic therapy in infants and children are also incompletely studied. This review will describe the kidney's role in the pathogenesis of sodium and water retention in heart failure and the developmental changes in the kidney related to fluid retention. Known principles of diuretic therapy in congestive heart failure will be described. All these factors can then be used by the reader to evaluate the role of diuretic therapy in the complex syndrome of heart failure in infants and children.