The link between the kidney and hypertension has been considered a villain-victim relationship. High blood pressure levels are a well-recognized feature in chronic renal disease, but the ability of mild-to-moderate hypertension to produce renal insufficiency has been questioned. Nephrosclerosis, benign nephrosclerosis, and hypertensive kidney disease are terms that clinicians use when renal damage is thought to be secondary to essential hypertension. Many cases of end-stage renal disease are ascribed to so-called benign nephrosclerosis. This entity could actually be a primary renal disease affecting the preglomerular microvasculature, perhaps genetically mediated and ethnically influenced, and showing a heterogeneous clinical expression. African Americans suffer from nephrosclerosis more frequently than Caucasians. Nephrosclerosis affecting Caucasians seems to show a less aggressive pattern and could represent early age-related renal sclerosis. The risk of end-stage renal disease is increased when atherosclerotic lesions in large renal arteries coexist. Age, systolic blood pressure, proteinuria, and concomitant cardiovascular disease are well-known promoters of renal failure. A multifactorial strategy, including antihypertensive and antiproteinuric drugs, and lipid-lowering and anti-platelet agents, could improve cardiovascular and renal outcomes in patients with nephrosclerosis.