Low density lipoprotein (LDL) apheresis is one of the main therapeutic models for homozygous and severe heterozygous form of the familial hypercholesterolemia patients. Anti-atherogenic, anti-thrombogenic and anti-inflammatory effects of apheresis has positive effects on prevention of cardiovascular disease by improving of the tissue perfusion. Blood LDL cholesterol levels, response to medical therapy, presence or severity of the coronary heart disease are the main determinants of the apheresis indications. Except bleeding tendency and heparin sensitivity, there are no contraindications. In parallel with low body weight, pediatric practice could be more risky; however, there is also a 3.5-year-old apheresis application without problems. The first successful plasmapherisis for the removal of LDL cholesterol in circulation was performed in 1975. Plasmapheresis, today, is only emergency treatment model in cases of life-threatening hyperchylomicronemia. New apheresis techniques have rather high selectivity for atherogenic lipoproteins containing apolipoprotein-B100. If existing apheresis technique has low effectiveness (acute decrease of LDL cholesterol <60%), primarily calculated plasma or blood treatment volumes could be increased and then technique could be switched to other one. Early identification of the affected patients and aggressive LDL apheresis treatment significantly reduce the burden of cardiovascular disease in children and adult patients with homozygous or severe heterozygous familial hypercholesterolemia.