The renin angiotensin aldosterone system (RAAS) inhibitors induce an incomplete blockade of the system at different steps. Recently, the dual RAAS therapy is emerging in clinical practice, although there is a lack of evidence on safety and efficacy for this combination in several cardiovascular diseases. In this review, we evaluated the advantages and disadvantages of dual RAAS blockade in hypertension, proteinuric renal disease, heart failure and ischaemic heart disease. The role of DRIs in combination with ACEI or ARBs is promising, but still needs further studies. On the basis of the clinical outcomes and safety data the recommendations guidelines have not confirmed indications to dual RAAS blockade in essential hypertension treatment, heart failure and ischemic heart disease. Only proteinuric nephropathies and resistant hypertension may represent possible indications to dual RAAS blockade. Actually, rational combinations of either an ACEI or ARB or DRI with other classes of antihypertensives offer best solutions.