Multiple sclerosis (MS) is a dys-immune disease of the central nervous system with highly variable and unpredictable long-term outcome. In the early 1970s association between HLA alleles and MS was established. Very recently, the power of Genome Wide Association Studies (GWAS) enabled the identification of several loci involved in immune functions as genetic risk factors in MS. Recent data suggest that common genetic variations might modulate the clinical phenotype of MS through a regulation of key pathophysiological pathways. Identification of modifier genes might offer an opportunity to explore new relevant therapeutic targets and early prognostic markers. To date, studies of modifier genes in MS are numerous but results are still unclear. This research field may now benefit from large cohorts of patients available for association studies. In this context, we propose a review of epidemiological and association studies of genetic modifying effect in MS. Copyright © 2011 Elsevier Masson SAS. All rights reserved.