Despite multi-drug therapy, hypertension remains uncontrolled in a significant amount of patients, especially those with multiple cardiovascular risk factors. Endothelin-1 is a long lasting and very potent vasoconstrictor and plays a key role in cardiovascular hemostasis. Endothelin mediates its biological activity in humans through the endothelin A and B receptors. The selective endothelin--A receptor antagonist darusentan may be a new treatment option in patients with resistant hypertension. The objectives were that the clinical experience and the evidence for therapy with darusentan in resistant systemic hypertension were reviewed. The methods by the authors were that the leading journals which publish basic science and clinical research in the area of cardiovascular diseases and PubMed were scanned. In conclusion, early clinical results from Phase II studies suggest that darusentan may find a place in the treatment of resistant hypertension.