Chronic kidney diseases (CKD) are often progressive and usually associated with a relatively slow loss of function. This principally offers the opportunity for drug interventions over a prolonged period. The prerequisite is that clear therapeutic targets can be identified. One of the most important targets is the renin-angiotensin-aldosterone system (RAAS), the activation of which is a key contributor to the progression and deterioration of renal function. This article reviews the pathomechanistic principles of RAAS-mediated renal damage and the pharmaceutical possibilities for inhibition of the RAAS. The evidence from clinical studies on nephroprotection is summarized and the international guideline recommendations are discussed. As a future perspective, the novel possibility of a combined add-on treatment with nonsteroidal mineralocorticoid receptor antagonists is discussed based on the FIDELIO-DKD study.