The mineralocorticoid hormone aldosterone is essential in regulating the body’s salt and water balance. However, abnormal activation of the mineralocorticoid receptor (MR) by elevated levels of aldosterone and salt imbalance cause hypertension and other effects detrimental to the cardiovascular system. Thus, MR antagonists are expected to be beneficial to patients with high blood pressure and other cardiovascular diseases, such as heart failure. Until recently, only steroidal MR antagonists have been developed for therapeutic use. However, due to complexity in chemical synthesis, limited scope for selectivity versus other steroid hormone receptors, and undesirable physical and chemical properties, appropriate steroidal compounds have been difficult to identify and develop. Despite > 40 years of research, only two major steroidal MR antagonists, spironolactone and eplerenone, have been brought to the market for the treatment of hypertension and heart failure. Novel classes of non-steroidal MR antagonists h...