The association of low doses of perindopril and indapamide in a single pill has been developed to meet the criteria required for a fixed-dose combination to be used as first-line therapy. The experience accumulated so far has demonstrated a greater antihypertensive efficacy of this preparation compared with various monotherapies, but not at the expense of a worsening of tolerability. The perindopril/indapamide combination is particularly effective in lowering systolic and pulse blood pressure. Starting treatment with this fixed-dose combination improves arterial stiffness and allows a better regression of cardiac hypertrophy than angiotensin-converting enzyme-inhibition or beta-adrenoceptor blockade alone. In hypertensive patients with Type 2 diabetes, a greater reduction of urinary albumin excretion can be obtained with the perindopril/indapamide association compared with an angiotensin-converting enzyme inhibitor administered as monotherapy. There is evidence that a first-line management of hypertension based on a low-dose perindopril/indapamide combination can provide a better efficacy/safety ratio than other well-established therapeutic strategies.