This image portrays the anatomical relationships of the endothelium, intima, media, and adventitia. Each of these layers play an important role in the development of atheroscleropathy. Since the discovery of the essential role of an intact endothelium for the vasomotor control of musculo-elastic arteries by Furchgott and Zawadski in 1980, and the discovery of the NOSs in 1989, the endothelium has been found to play a central role in the maintenance of healthy arteries and found to be placed in a central role for the development and progression of atherogenesis and subsequent atheroscleropathy. The endothelium is five times the weight of the heart and equal to the weight of the liver. This organ is placed at a critical location as an interface with nutrients and toxic products not only at its luminal side of musculo-eleastic arteries but also at the endothelial extracellular matrix interface at the site of capillaries. This exciting monolayer of unique cells is responsible for the production of a gas NO that acts to modulate blood flow and is a naturally occurring interfacing antioxidant capable of scavenging ROS. The intima, sandwiched between the internal elastic lamina of the medial smooth muscle cell layer and the endothelium is the site of atherosclerosis, intimopathy, and the atheroscleropathy associated with MS, IR, PD, and T2DM. The injurious stimuli depicted on the luminal side of the endothelial cell (including redox and oxidative stress with ROS) result in the adaptive changes in which we are familiar: Remodeling of the arterial vessel wall: From Atheroma to Atherosclerosis, to Atheroscleropathy: A MALIGNANT TRANSFORMATION.