Diuretics are used in various conditions with fluid overload. Their efficacy in the management of congestive heart failure is well documented. In contrast, the indication of diuretics in chronic lung disease and central nervous system disorders of the newborn have not been clearly established. Substantial pharmacologic knowledge of diuretics in the young infant remains to be described. Most investigations on diuretics in the sick newborn infant have examined furosemide. In contrast, the pharmaco-dynamics, pharmacokinetics, clinical indications, and toxicity of other diuretics used in the newborn require considerable further evaluation. Future studies using a combination of diuretics, acting at different segments of the nephron, also may provide newer therapeutic modalities to overcome or prevent the development of frequently observed tolerance to diuretics, as well as to treat refractory edema.