The morphological findings of so-called hypertensive nephrosclerosis, rather than implying a linear direct relationship to damage induced by hypertension, may indicate complex environmental and genetic factors, which together foster the coexistence of renal lesion and hypertension in this clinical setting. We discuss the clinical and pathological criteria for diagnosis of arterionephrosclerosis, and possible pathogenetic factors, including hypertension, ethnicity, aberrant autoregulation, prothrombotic mechanisms, low birth weight, decreased nephron number, genetic factors and dysmetabolic syndrome.