This review summarizes current knowledge on the pharmacology, pharmacokinetics, pharmacodynamics, and clinical application of the most commonly used diuretics in children. Diuretics are frequently prescribed drugs in children. Their main indication is to reduce fluid overload in acute and chronic disease states such as congestive heart failure and renal failure. As with most drugs used in children, optimal dosing schedules are largely unknown and empirical. This is undesirable as it can potentially result in either under- or over-treatment with the possibility of unwanted effects. The pharmacokinetics of diuretics vary in the different pediatric age groups as well as in different disease states. To exert their action, all diuretics, except spironolactone, have to reach the tubular lumen by glomerular filtration and/or proximal tubular secretion. Therefore, renal maturation and function influence drug delivery and consequently pharmacodynamics. Currently advised doses for diuretics are largely based on adult pharmacokinetic and pharmacodynamic studies. Therefore, additional pharmacokinetic and pharmacodynamic studies for the different pediatric age groups are necessary to develop dosing regimens based on pharmacokinetic and pharmacodynamic models for all routes of administration.