Mineralocorticoid receptor antagonists (MRA) can reduce cardiovascular morbidity and mortality in patients with heart failure and ischemic heart disease. In addition, these agents have been used in patients with diabetic nephropathy to control proteinuria and slow down chronic kidney disease (CKD) progression. Current guidelines recommend against the use of MRAs in patients with advanced CKD. However, there is growing interest on their use in this population that has unmet needs (high cardiovascular morbidity and mortality) and unique challenges (risk of acute kidney injury or hyperkalemia). This narrative review discusses the emerging role of MRAs for the management of cardiovascular disease and/or the prevention of CKD progression, highlighting results from randomized controlled trials and presenting real-world data from available registries. Results from recent trials in patients on maintenance dialysis are also discussed.