Endothelin 1 (ET-1) is extremely potent vasoconstrictor with long-lasting effects in the human cardiovascular system. ET-1 is mostly produced in vascular endothelium including heart and kidney where ET-1 is persistently generated in blood vessels to maintain blood pressure and vascular tone. ET-1 can regulate renal hemodynamics by alteration of glomerular capillary pressure and glomerular filtration.  ET-1 can constrict afferent arteriole via endothelin receptor type A (ETA) and endothelin receptor type B (ETB). And ET-1 can modulate efferent arteriolar tone via ETA and is balanced by ETB effects to produce vasodilation. ET-1 is associated with proteinuria and podocyte dedifferentiation. ET-1 can lead to podocyte ultrastructural degeneration and contribute a further breakdown of glomerular filtration barrier. In the interstitium, ET-1 can promote interstitial fibroblast proliferation and generation of extracellular matrix via ETA. On the other hand, ET-1 is generated by medullary collecting duct cells, where ET-1 blocks the vasopressin stimulated water retention, leads to natriuresis and diuresis. The natriuretic effect of ET-1 is related to nitric oxide production via ETB. Endothelin receptor antagonist (ETA) can be effective in hypertension, heart failure, cerebral hemorrhage and kidney disease on the basis of ET-1 action. In kidney disease, ETA can be effective in improving glomerular hypertension, proteinuria and fibrosis. However, ETA can cause vasodilator effects such as headache and hypotension, fluid retention and edema. In the early work of non-selective ETA, which inhibit both ETA and ETB, ASCEND trial was terminated after median 4 months of follow up due to higher cardiovascular events such as volume overload, heart failure and death although albuminuria was reduced significantly in patients with diabetic nephropathy. However, recent trials of selective ETA have been shown promising results in kidney disease.  In SONAR trial, atrasentan (ETA:ETB selectivity 1800:1) significantly lowered a primary composite renal endpoint event during median follow-up was 2·2 years. Adverse events such as fluid retention and anemia were more frequent in atrasentan group than placebo, however, hospital admission for heart failure and death was not different between groups. In DUET study, sparsentan (ETA:ETB selectivity 1000:1) achieved significantly greater reductions in proteinuria after 8 weeks compared with irbesartan in FSGS patients. Edema and hypotension were more common among sparsentan group but did not result in study withdrawals. Fluid retention and edema of ETA might be effectively managed by adding sodium glucose co transporter 2 inhibitors to an ETA in recent post-hoc analysis of SONA trials. Further phase III clinical trials of selective ETA are ongoing in patients with IgA nephropathy and other kidney disease.