LDL-cholesterol is the leading risk factor which influences the clinical outcome of patients with preexisting coronary heart disease. Clinical trials show that plasma LDL-cholesterol below 100 mg/dL decrease the rate of recurrent myocardial infarction and can induce regression in patients with coronary heart disease. However, in most cases of severe hypercholesterolemia with plasma LDL-cholesterol concentrations above 220 mg/dL LDL cannot be sufficiently decreased by maximal dietary and pharmacological therapy alone. Today this group of high risk CHD patients can be treated in addition with an extracorporeal procedure to eliminate LDL from the plasma circulation, the H.E.L.P.--LDL-apheresis. This method for selective removal of LDL, lipoprotein(a) and fibrinogen from plasma has been shown to be a clinically safe and very efficient method for the treatment of patients with homozygous familial hypercholesterolemia or CHD patients with severe hypercholesterolemia. Treatments with 1 week H.E.L.P. intervals revealed a mean reduction of minus 51% for LDL, of minus 45% for Lp(a) and of minus 46% for apo B, while HDL was increased by +12%. Fibrinogen was decreased by minus 46%. Besides the marked reduction of LDL and fibrinogen plasma concentrations the H.E.L.P. treatment significantly improves hemorheological parameters and increases the oxygen tension in the tissue. We have also investigated the efficiency of a combined therapy, using HMG-CoA reductase inhibitors together with the H.E.L.P.--apheresis. Under this combined treatment, a reduction of the interval LDL-cholesterol levels of 70-80% has been achieved, while Lp(a) and fibrinogen were not further affected. We now report about our long-term clinical experience with the H.E.L.P. system in treating patients with different lipoprotein disorders: (1) Homozygous form of familial hypercholesterolemia; (2) CHD patients with familial and non-familial hypercholesterolemia; (3) CHD patients with very high concentrations of lipoprotein(a); and (4) Hypercholesterolemic patients after heart transplantation. Based on present experience guidelines for secondary prevention of coronary heart disease indications for the H.E.L.P.--LDL-apheresis treatment are discussed.