LDL apheresis (LDLa) is an invasive therapeutic tool to control qualitative and quantitative disorders of lipid metabolism. It is aimed at achieving a metabolic balance in association with lipid-lowering drugs in patients with severe, genetically determined or acquired dyslipidemia who do not reach clinically adequate LDL-cholesterol (LDL-C) levels (<70 mg/dL) despite appropriate lipid-lowering drug treatment. A poorly known dyslipidemia is constituted by elevation of lipoprotein (a) [Lp(a)], which appears to be genetically determined and not influenced by diet or lipid-lowering medication. An Lp(a) level exceeding 30 mg/dL is an independent risk factor for premature cardiovascular disease and cerebrovascular disease. Numerous data support the notion that cardiovascular risk reduction is related to the degree of reduction of LDL-C, and the progression of atherosclerosis can be delayed or reversed by intensive and continuous cholesterol-lowering treatment. After the introduction of HMG-CoA reductase inhibitors (statins), the clinical benefit of cholesterol-lowering treatment has received significant confirmation. However, this treatment has shown poor results in the most severe, genetically determined forms. LDLa is an intensive extracorporeal cholesterol-lowering treatment approach with well documented efficacy and safety. It has also shown effects not directly correlated with its lipid-lowering activity, such as antioxidant effects on oxidized LDL and antiinflammatory effects on the cytokine network, the endothelium and the coagulation system. Finally, data acquired by the Italian Multicenter Study on LDLa Working Group were highlighted and the new evidence in the literature discussed.