Treatment resistant hypertension is defined as a blood pressure not achieving a goal blood pressure (< 140/90 mm Hg). The diagnosis of resistant hypertension requires use of good blood pressure technique to confirm persistently elevated blood pressure levels. Pseudoresistance, including lack of blood pressure control secondary to poor medication adherence or white coat hypertension, must be excluded. The evaluation of patients with resistant hypertension is focused on identifying contributing and secondary causes of hypertension which are guided by the clinical feature of hypertension: metabolic (obstructive sleep apnea, kidney disease), vascular (renal artery atheroma stenosis), endocrine (hyperaldosteronism), familial (renal artery fibrodyspalsia, adrenal causes). Treatment includes removal of contributing factors, appropriate management of secondary causes, and use of effective multidrug regimens. Three antihypertensive medications including ARB or ACEI in addition to calcium channel blocker and to thiazide diuretics is able to control 75% of hypertensive subjects when prescribed in effective doses. The addition of low dose spironolactone to this triple treatment induces significant BP reduction in most patients with resistant hypertension.