Despite the presence of seven different antihypertensive drug classes and over 120 different antihypertensive medications, about 48 % of the 75 million people with hypertension are not reaching their target blood pressure goals. One of the reasons for this lack of control is the failure to adequately inhibit the sympathetic nervous system. Consequently, alternative therapies have been attracting interest. Recent technical advances targeting the sympathetic over-activity of the carotid sinuses (baroreflex activation therapy, BAT) and the renal sympathetic nerves (renal denervation therapy, RDT) have renewed interest in invasive therapies for the treatment of drug-resistant hypertension. Encouraging results from the recent Rheos Pivotal and Symplicity HTN-2 trials on the safety and efficacy of BAT and RDT, respectively, indicate that invasive approaches can safely reduce blood pressure in patients with resistant/refractory hypertension. These approaches, while still experimental in the US, are appropriate for those on more than three fully tolerated doses of antihypertensive medications whose blood pressure is not at goal, i.e. <140/90 mmHg. The present review is focused on the clinical implications of these two technics and when they are appropriate.