Treatment-resistant hypertension, or resistant hypertension, is defined as blood pressure that remains above target despite concurrent use of at least three antihypertensive agents from different classes at optimal doses, one of which should be a diuretic. Important considerations in the diagnosis of treatment-resistant hypertension include the exclusion of pseudoresistance and the evaluation of potential secondary causes of hypertension and of concomitant conditions that maintain high blood pressure. The ability to diagnose true treatment-resistant hypertension is important for selection of patients who may be appropriately treated with an invasive therapy. Currently, there are three interventional approaches to treat resistant hypertension, namely: (1) reduction of the activity of the sympathetic nervous system by renal nerve ablation, (2) stimulation of baroreceptors and (3) creation of a peripheral arterial venous anastomosis. This review focuses on the rationale behind these invasive approaches and the clinical results.