Rheopheresis comprises various types of apheresis procedures, namely double filtration plasmapheresis, LDL apheresis, and fibrinogen apheresis. These techniques are used to remove high molecular weight proteins from the circulation and have been shown to exert a protective effect on the vessel walls. The vascular protection can be attributed to pleiotropic mechanisms, especially from LDL apheresis, that safeguard against endothelial dysfunction by reducing the concentrations of proinflammatory and procoagulation factors. In addition, rheopheresis improves whole-blood viscosity, principally by reducing fibrinogen and lipoproteins, stimulates endothelium-mediated vasodilation, and has a positive effect on the hemorheological picture, improving perfusion in the microcirculation. All of this helps to correct the functional vessel alterations caused by aggression factors, and is translated into an extremely fast clinical response, only a few hours after the end of apheresis. Demonstrated efficacy has been obtained especially in the microcirculation, as has been observed in ischemic optic neuropathy, sudden hearing loss, and peripheral arterial disease. Although the short-term effects on the functional component of the vascular damage seem to be temporary, long-term effects on the morphological alterations have been shown. It is still not clear which of the many suggested actions, or others still to be confirmed (for instance a short-term increase in endothelial progenitor cells) constitutes the main vessel protective mechanism.