Thiazide-type diuretics are commonly used in the treatment of hypertension and nephrolithiasis. Evidence from randomized clinical trials needs to be considered in decisions about agent choice and dose. In nephrolithiasis, one of the major limitations of the literature is a paucity of data on the dose-response effect of hydrochlorothiazide (HCTZ) on urinary calcium excretion. The best available evidence for prevention of stone recurrence suggests the use of indapamide at 2.5 mg/d, chlorthalidone at 25 to 50 mg daily, or HCTZ 25 mg twice a day or 50 mg daily. In hypertension, chlorthalidone (12.5 to 30 mg daily) may be the best choice when a diuretic is used for initial therapy, with indapamide (1.5 mg daily) being a valuable alternative for older patients. When adding a thiazide to other drug classes, indapamide (2.5 mg daily) has demonstrated value in hypertensive patients who have had a stroke, and HCTZ (12.5 to 25 mg daily) has a safe track record in several patient groups. Although chlorthalidone has not been tested as add-on therapy, the authors believe it is a safe option in such cases.