Renal sympathetic denervation (RDN) has been proposed as a new treatment modality in patients with apparent treatment-resistant hypertension (TRH), a condition defined as persistent blood pressure (BP) elevation despite prescription of at least three anti-hypertensive drugs including a diuretic. However, the large fall in BP reported after RDN in Symplicity HTN-2, the first randomized study, and in multiple observational studies has not been confirmed in five subsequent prospective randomized studies. The reduction in BP may be mostly due to non-specific effects, such as improvement of drug adherence in initially poorly adherent patients (the Hawthorne effect), placebo effect and regression to the mean. The overall BP lowering effect of RDN seems rather limited and the characteristics of the true responders remain largely unknown. Accordingly, RDN is not ready for clinical practice. In most patients with TRH, drug monitoring and subsequent improvement of drug adherence may prove more effective and cost-effective to achieve BP control. In the meantime, research should aim at identifying characteristics of those few patients adherent to drug treatment who has TRH and may respond to RDN.