Aldosterone antagonists have been highly successful in treating congestive heart failure and resistant hypertension. Until recently, therapies targeting the mineralocorticoid receptor in chronic kidney disease (CKD) have received little attention, largely because of the risk of hyperkalemia and the incorrect assumption that traditional therapy with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or both consistently reduces activity of the renin-angiotensin system in all patients. Control of extracellular volume and low-dose mineralocorticoid receptor blocker therapy may offer additional antihypertensive and anti-inflammatory benefits in select CKD populations.