Although traditional approaches are effective for the treatment and control of hypertension, they have not succeeded in curing the disease, and have therefore reached a plateau. As a result of the completion of the Human Genome Project and the continuous advancement in gene delivery systems, it is now possible to investigate genetic means for the treatment and possible cure for hypertension. In this review we discuss the potential of genetic targeting of the renin-angiotensin system for the treatment of hypertension. We provide examples of various approaches that have used antisense technology with a high degree of success. We focus on our own research, which targets the use of antisense of the angiotensin type I receptor in various models of hypertension. Finally, we discuss the future of antisense technology in the treatment of human hypertension.