OBJECTIVES Although apheresis is an important treatment for reducing LDL-C in familial hypercholesterolemia (FH) patients, little is known about its treatment patterns. We conducted a systematic review to assess the efficacy/effectiveness, practice patterns, cost, and clinical guidelines for apheresis in FH patients.  METHODS Electronic databases were searched for publications of apheresis in FH patients. Inclusion criteria include: articles in English published 2000-2013, description of practice patterns, efficacy/effectiveness, and costs. Data were stratified by country and FH genotype where possible.  RESULTS Thirty-seven studies met the inclusion criteria: 8 open-label clinical trials, 11 observational studies, 16 reviews/guidelines, and 2 health technology assessments. Of the 19 clinical and observational studies, 6 assessed only homozygous FH (HoFH) patients, 4 assessed only heterozygous FH (HeFH) patients, 6 included HoFH and HeFH patients, and 3 did not specify type of FH. The prevalence of FH is not well characterized by country and underdiagnosis is a barrier to optimal FH treatment. Apheresis guidelines recommend weekly/bi-weekly treatments conducted at apheresis centers that may last ≥ 3 hours per session. Apheresis may be recommended as first-line treatment in HoFH patients and after drug therapy failure in HeFH patients. Studies reported a range of LDL-C reduction after apheresis: HoFH: 57-75%; HeFH: 58-63%. Eight studies reported apheresis costs. Cost (USD 2013) per apheresis session ranged from $2,200-$4,300 in the US, $2,150-$2,600 in the UK, $1700-$1850 in Germany and France, and $2,350-$2,750 in Australia. Calculated annual costs may reach $88,400-$225,000 per patient for weekly treatment.  CONCLUSIONS LDL-C apheresis treatment is necessary for FH patients when drug therapy is inadequate. While apheresis reduces LDL-C, high per-session costs and the frequency of guideline-recommended treatment result in substantial annual costs. The costs and the inconvenience of apheresis sessions are barriers in optimal treatment of FH.