In this issue of the Journal, Shlomai, Grassi, Grossman,and Mancia address the always “hot topic” of targetorgan damage in patients with hypertension in an articleentitled “Assessment of Target Organ Damage in theEvaluation and Follow-Up of the Hypertensive Patients:Where Do We Stand?” The article is thoughtful andinformative, considers the facts and takes away thefiction, and balances the totality of evidence to reachconclusions. It is a pleasure to offer my brief commen-tary from a different angle.Hypertension is a well-known cardiovascular (CV)risk factor that contributes substantially to increasedmorbidity and mortality. High blood pressure (BP) cancause changes in many organs in the body, such as leftventricular hypertrophy (LVH), proteinuria and renalfailure, retinopathy and vascular dementia, increasedcarotid intima-media thickness, and even increasedcalcium score. These changes are collectively called“target organ damage” (TOD) and are associated withincreased risk for CV complications. There are manyprocesses involved in the pathogenesis of TOD andthese include endothelial activation, platelet activation,increased thrombogenesis, changes in the renin-angiotensin-aldosterone system (RAAS), and collagenturnover. Most of the changes early on affect thevasculature, cause endothelial dysfunction, vascularhypertrophy, arteriosclerosis, and atherosclerosis. Forthis reason, hypertension has also been called a vasculardisease.Endothelial dysfunction (or endothelial activation) ischaracterized by 3 distinct properties: inability tovasodilate, inability to prevent adhesion of inflamma-tory molecules, and loss of ability to prevent proteinleak.Endothelial dysfunction is associated with decreasedproduction of nitric oxide (NO) and decreased NObioavailability in the vessel wall