Hypertension, which is one of the most common diseases afflicting mankind, is associated to increased morbidity, mortality and cost to society. Cardiovascular disease is the leading cause of death all around the world and hypertension is the most common reversible risk factor for cardiovascular diseases. The renin-angiotensin system (RAS) commands an important role in the regulation of blood pressure, and so, at present, has been a target for clinical control by drugs acting on the system. Despite the fact that effective drugs are available, only about one out of three people has their blood pressure successfully controlled, and the blame goes to the undesirable side effects and the poor oral drug compliance. Keeping in mind the increasing incidence of hypertension and the patients' inconsistency for the polypharmacy, immunization against renin and the angiotensins, although with less success, had been attempted in the past. More recently, immunization against angiotensin-I with PMD-3117 vaccine, angiotensin-II with CYT006-AngQb vaccine and targeting angiotensin-II type 1A receptor with ATR12181 vaccine have provided optimism in the development of a hypertension vaccine. AngQb vaccine has proved to become the first vaccine ever to lower(-9/-4 mm Hg) blood pressure in human beings. Vaccine could induce long lasting effects with a dosing interval of months, increasing patient acceptability and compliance and thus a better control of high blood pressure. Our objective will be to focus on the importance of the RAS and to explore the extent of safety, efficacy and the future implications of vaccine against the RAS. (c) 2009 Elsevier Ireland Ltd. All rights reserved.