The indications for chlorthalidone are roughly identical to the ones for thiazides: these diuretics are a suitable basis for the long-term treatment of arterial hypertension. About 50% of the patients with mild hypertension are treated sufficiently only on the basis of a diuretic such as chlorthalidone. Small doses (12.5 to 25 mg/day) already have an optimal effect; higher doses cause more side-effects. If its effects are insufficient, chlorthalidone can easily be combined with other antihypertensive agents. The advantages of a diuretic treatment is well documented particularly in relation to moderate and severe hypertensions: heart disease, strokes, aortic aneurysms and renal failures are thus reduced. In elderly people with isolated systolic hypertension, chlorthalidone not only reduces the incidence of strokes but also of myocardial infarctions.

The effect of chlorthalidone is well documented for mild and moderate heart disease, as well as edemas preceded by a nephrotic syndrome.

Chlorthalidone also has proven effect against diabetes insipidus and it can be prescribed for the treatment of hypercalciuria with relapsing nephrolithiasis. Some authors also recommend chlorthalidone for the treatment of Ménière's disease.

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