Diuretics, which are primarily used to modify the volume and the composition of body fluids, are widely used to treat hypertension. The diuretics include a) the thiazides and thiazide-like agents, which are the most common drugs used to treat high blood pressure (these drugs inhibit sodium reabsorption in the early distal convoluted tubule); b) loop diuretics, such as furosemide, block chloride and sodium reabsorption by inhibition of the Na+/K+/2Cl− cotransport system in the thick ascending limb of the loop of Henle; and c) potassium-sparing (retaining) diuretics, including aldosterone receptor blockers (such as spironolactone and eplerenone) and epithelial sodium channel blockers (such as amiloride and triamterene, which interfere with the reabsorption of sodium and excretion of potassium and hydrogen that takes place in the late distal tubule, the connecting tubule, and the cortical collecting duct). Hydrochlorothiazide 12.5 mg once daily or equivalent low dosages of other similar agents reduce blood pressure in approximately one-half to two-thirds of patients who are responsive to this class of drugs; higher doses add little to the effect on blood pressure and also increase side effects. Some combinations of very small doses of thiazide diuretics-for example, 6.25 mg hydrochlorothiazide or 0.625 mg indapamide, with a low dose of an antihypertensive drug of a different class-have average antihypertensive efficacy when used once daily. Furosemide is used in patients with renal failure or severe heart failure and is best given by continuous intravenous infusion. The potassium-sparing diuretics are generally used in combination with thiazide diuretics to treat hypertension. Side effects occur at about the same frequency and severity with equipotent doses of all diuretics. The incidence of side effects is dose-dependent and also increases as a function of the duration of the renal excretory and antihypertensive actions. However, longer-acting diuretics provide better 24-hour control of blood pressure and increase compliance and adherence to the treatment regimen.