This section discusses the reasons different diuretic agents inhibit salt reabsorption at specific sites within the renal tubule. It also includes a brief review of how diuretics reach their target site of action along the nephron, together with a discussion of how disease states may affect the delivery of diuretics to those sites. When diuretics are administered to edematous patients, the natriuretic response is often blunted. In addition, increased renal tubular salt avidity is observed after administration of loop diuretics. The elements required to successfully achieve adequate natriuresis under such conditions are analyzed. Because achieving diuresis may result in significant hypokalemia, hyponatremia, metabolic alkalosis, and worsening prerenal azotemia, the prevention and management of these complications of diuretic therapy are also reviewed. A description of successful use of diuretics in specific edematous states, such as congestive heart failure, chronic renal failure, nephrotic syndrome, and liver disease, is followed by a brief discussion of the management of resistant edema and the use of diuretics in nonedematous states, including essential hypertension and other conditions.