The function of vasa vasorum is both to deliver nutrients and oxygen to arterial and venous walls and to remove "waste" products, either produced by cells in the wall or introduced by diffusional transport through the endothelium of the artery or vein. Although the relationship between changes in vasa vasorum characteristics and the development of atheromatous plaques is well documented, the role of vasa vasorum, especially in terms of their appearance and disappearance in disease processes such as atherosclerosis, are still not clearly understood in terms of their being causative or merely reactive. However, even if their proliferation is merely reactive, these new microvessels may be a source of disease progression by virtue of endothelial impairment and as a pathway for monocytic cells to migrate to sites of early disease. As both these features are aspects of the vasa vasorum function, this Review focuses on the following issues: 1) acute modulation of vasa vasorum patency due to surrounding compressive forces within vessel wall and due to variable tone in the smooth muscle within proximal vasa vasorum and 2) chronic angiogenic responses due to local cytokine accumulations such as occur in the wall of arteries in the presence of hypertension, hypercholesterolemia, accumulation of lipids, extravasated blood products (e.g., red blood cells, macrophages, inflammatory products) which attract monocytes, and response of vasa vasorum to pharmacological stimuli.