The blockade of the renin-angiotensin system (RAS) improves the prognosis of patients with complications related to diabetes, hypertension or, in general, atherosclerosis. Several observational studies have suggested the use of a dual blockade of the RAS to benefit from a better cardiorenal protection. However, recent randomized controlled studies failed to demonstrate that a dual blockade exert a better protection than single blockade, but showed a higher risk for renal complications and hyperkalemia. To decrease the residual risk, other opportunities may be recommended such as reinforcement of low salt diet, use of supraphysiological dose of a monotherapy inhibiting the RAS (perhaps prescribed at the evening) or addition of an aldosterone antagonist. However, all these approaches, as dual therapy, may also increase the risk of hypotension and renal insufficiency and thus require to be used under strict medical supervision.