Hypertension and oedema resulting from sodium retention are the main indications for diuretic treatment in patients with chronic renal failure. The pharmacokinetics of most loop diuretics and their active metabolites are altered in chronic renal failure, due both to reduced transtubular transport via the proximal tubular anion transporter and to protein binding within the tubule. In chronic renal failure, the reduced number of nephrons leads to adaptive reduction of tubular sodium reabsorption, i.e. high baseline fractional natriuresis and increased absolute distal tubular sodium reabsorption. These processes interfere with the pharmacodynamic actions of diuretics. Therapeutic strategies to overcome the partial resistance to the action of diuretics in patients with chronic renal failure include the use of high doses, continuous administration and the combination of loop and thiazide compounds.