Vasa vasorum are microscopic vessels that perfuse the walls of macroscopic arteries and veins. Numerous observations over the years underpin the speculation that vasa vasorum play a significant role in arterial disease. For instance, atheromatous plaques tend to form in arteries that normally have vasa vasorum, when there is damage to the outer adventitia or when vasa vasorum are ligated. Although, atheromatous plaques do form in small arteries that do not initially have vasa vasorum - they do so only when the plasma concentrations of lipids are exceptionally high, such as occurs in LDL-/- apoE-/- double knockout mice. Recent developments in micro-CT imaging provide 3D images of intact segments of arteries and therefore can now provide heretofore inaccessible information. Examples are the perfusion territory size and location of individual vasa vasorum “trees” as well as an index of the spatial distribution of solute diffusion into, and washout from, the arterial wall. In addition, several types of genetically modified “knockout” mice that have recently been developed have a propensity for developing atheromatous plaques and vasa vasorum and thereby serve as powerful tools to further examine the biomolecular and genetic aspects of atheroma development and the response to interventions.