Lipid apheresis effectively lowers LDL-cholesterol even in drug-unresponsive severely hypercholesterolemic patients. This results in improvement of symptoms of coronary artery disease, reduces progression of coronary atherosclerosis, and decreases coronary event rates. Besides aggressive lipid lowering itself, these effects may also be due to nonselective removal of other high molecular weight proteins leading to improved hemorheology. Lipid apheresis is also used for treating symptoms of vascular diseases outside the coronary arteries, such as peripheral arterial disease and the angioneuropathic diabetic foot syndrome. This review discusses putative effects of lipid apheresis and rheophereis on restoring pathophysiological processes involved in the development of symptoms of peripheral arterial disease, critical limb ischemia, and the diabetic foot syndrome. The clinical experience with lipid apheresis and rheopheresis in treating patients with peripheral arterial disease and the diabetic foot syndrome is critically reviewed and put into the context of currently available established treatment options. Based on this analysis, the limitations of current evidence are discussed and potential fields of research are suggested.