Unrelated disease processes commonly occur in non-diabetic individuals with mild-to-moderate hypertension and low level or absent proteinuria who present with chronic kidney disease: primary glomerulosclerosis in those with recent African ancestry, and arteriolar nephrosclerosis with resultant glomerular ischaemia potentially related to hypertension and vascular disease risk factors in other cases. Unfortunately, nephrologists often indiscriminately apply a diagnosis of 'hypertensive nephrosclerosis' to patients in either scenario, which implies that the hypertension is causative of their renal disease. Although nephropathies that are associated with variants in the apolipoprotein L1 gene (APOL1) often cause secondarily elevated blood pressure, they belong to the spectrum of focal segmental glomerulosclerosis and are not initiated by systemic hypertension. Because genetic testing for APOL1 variants and other glomerulosclerosis-associated gene variants is available and can provide a precise definition of disease pathogenesis, we believe that the term 'hypertensive nephrosclerosis' should now be abandoned and replaced with either gene-based (for example, APOL1-associated) glomerulosclerosis or arteriolar nephrosclerosis. Precision medicine will be key to improving diagnostic accuracy in this field. Discrimination of these disparate disorders has the potential to eradicate primary forms of glomerulosclerosis that are associated with APOL1 renal-risk variants.