The pathogenic role of angiotensin II (ANG II), dietary sodium chloride, sympathetic activation, obesity and aldosterone in the development of structural vascular changes (SVCs) in hypertension is considered from three perspectives (criteria): their utility in predicting hypertension and its complications (predictability); the effect of their inhibition or removal on the reversal of SVCs (reversibility); and their ability to induce SVCs in experimental animals (reproducibility). Only ANG II meets all three criteria. Importantly, ANG II increases preglomerular vascular resistance by inducing structural changes in renal cortical resistance arteries and arterioles. High salt intake, by dilating and thereby stiffening some arteries, may play a role in the development of systolic hypertension with aging, but does not produce structural changes in renal cortical resistance vessels. While high circulating levels of norepinephrine are associated with SVCs, the experimental evidence for the role of sympathetic nerve stimulation in the development of SVCs is inconclusive. Obesity is associated with hypertension, but is not known to be associated with SVCs. Salt-loading is required for aldosterone to produce SVCs, but vascular pathology in this experimental model differs from that in benign essential hypertension. The findings of this review indicate that SVCs in extra-renal sites by themselves do not lead to hypertension; structural changes in renal cortical arteries and arterioles that increase preglomerular vascular resistance are needed. Progressive trophic stimulation of preglomerular resistance vessels by itself may lead to hypertension. ANG II is prime candidate for such stimulus.