To report the case of a patient with resistant hypertension, in whom antihypertensive therapy was instituted by sequential nephron blockade. After an initial evaluation, the patient received as an additional prescription to the baseline regimen (losartan, chlorthalidone and amlodipine), spironolactone, furosemide and lastly amiloride, sequentially to increase the natriuretic effect. The patient performed ambulatory blood pressure monitoring (ABPM) 24 hours before and 12 weeks after starting treatment. A review of the literature and this case report revive the discussion of the treatment of a rather complex clinical entity, that is, resistant hypertension. When sequential nephron blockade is well instituted in patients with a correct diagnosis of resistant hypertension, excluding secondary causes, pseudo-resistance and associated factors such as poor adherence to treatment, it provides satisfactory and permanent control of blood pressure with improved quality of life.