Mineralocorticoid receptor antagonists (MRAs) have been effective in reducing total mortality in patients with heart failure (HF) and a reduced left ventricular ejection fraction. Due to the finding that aldosterone levels decrease with age, one might question the effectiveness of MRAs in very old patients (≥80 years of age), those at the greatest risk for developing HF with a preserved left ventricular ejection fraction (PEF). However, while aldosterone levels decrease with age, there is also a decrease in the enzyme 11 beta HSD2 levels with age, thereby allowing cortisol to stimulate the mineralocorticoid receptor (MR), which in younger patients with higher levels of 11 beta HSD 2 levels is converted to cortisone which cannot activate the MR. There is also an increase in the expression of the MR in the vascular wall with age. Thus, there is reason to believe that MRAs might be effective in reducing cardiovascular mortality and the incidence of hospitalizations for HF in very old patients with HFPEF. There is also reason to believe that MRAs might favorably affect many of the comorbid conditions associated with HFPEF in very old patients. The safety and efficacy of this hypothesis is currently under investigation in the NHLBI sponsored TOPCAT trial.