Chronic activation of the renin-angiotensin system (RAS) plays a crucial role in the development of various cardiovascular diseases (CVD). Thus, effective RAS inhibition has been a major achievement to improve the treatment of patients at risk for CVDs, such as myocardial infarction, heart failure and stroke. Three substance classes that block RAS-activation are currently available, angiotensin converting enzyme (ACE) inhibitors, angiotensin II type 1 receptor blockade (ARB) and renin inhibitors. Although the overall goal of these drugs remains the blockade of RAS activation, their individual targets in this system vary and may substantially influence the clinical benefit derived from the long term use of these substances. Here, we summarize the evidence available for the use of ARBs in different cardiovascular pathologies and the impact of this evidence on current treatment guidelines for patients at risk for CVD. Today, ARBs represent a good alternative in case of ACE-inhibitor intolerance due to their outstanding tolerability. ARBs in comparison to ACE-inhibitors have been proven to exert similar effective in the treatment of systolic heart failure, primary prevention of stroke, new onset of diabetes mellitus (DM) type 2 and DM type 2 dependent macroalbuminuria. ARBs should be considered as alternatives to ACE-inhibitors in subjects post-myocardial infarction. Overall however, there is no profound proof for a specific cardiovascular protection by blockade of the angiotensin II Type 1 (AT1) receptor that exceeds the impact of ACE-inhibition or synergises with ACE-blockade. In fact, combination of ARBs and ACE-inhibitor result in an increased rate of adverse effects and, therefore, this combination should not be encouraged. To summarize, the initial hope for a more specific impact on cardiovascular diseases by inhibition of the AT1-receptor in comparison to ACE-inhibition has not come true. However, ARBs have been proven to be equally effective as ACE-blockade in a large variety of clinical settings.