This review summarizes the envolving role of L-arginine, the metabolic precursor of nitric oxide (NO), in disease states that produce progressive loss of kidney function. Hypertension and hypertensive nephrosclerosis manifested in the Dahl/Rapp salt-sensitive rat are exquisitely sensitive to oral L-arginine, which can completely prevent hypertension and subsequent renal damage in these rats. L-Arginine also has been shown to decrease glomerular sclerosis in the remnant kidney model and improve renal hemodynamics and function in animal models of diabetes mellitus. Finally, accumulation of inhibitors of NO production occurs in renal failure and may contribute to hypertension in these patients. Understanding the role of L-arginine and the L-arginine:NO pathway in diseases that produce progressive renal failure may provide new approaches to management.