Despite the attractiveness of a vaccination strategy for the treatment of high blood pressure, and many decades of research, attempts to translate this strategy to hypertension management have been unsuccessful. Immunization against components of the renin angiotensin system offers the prospect of improved long-term control of hypertension because efficacy does not require daily compliance with oral medication. Moreover, such a strategy may provide therapeutic benefits beyond blood pressure control, such as improved prevention and treatment of heart failure, and cardiovascular, cerebrovascular, and renal disease. However, despite these potential advantages, there are a number of concerns about the safety and efficacy of this approach. Renin immunization demonstrated effective blood pressure reduction in animal models of hypertension but was accompanied by autoimmune disease of the kidney. Moreover, there are theoretical arguments that angiotensin immunization may have limited effectiveness and clinical studies confirmed these limitations. Vaccination against the angiotensin II type 1 receptor is another possible approach but has yet to undergo clinical evaluation. Thus, the role of vaccination against renin angiotensin system components in hypertension management remains to be established.