A genetic contribution to the pathogenesis of MS has been proven by discovery of HLA-DR2 locus over 40 years ago and description of familial aggregation of MS. Novel array technologies in parallel with analytical tools, improved central sample collection in MS centres and intensified international collaborations have led to the identification of a number of new MS risk alleles, all with a minor effect. The odds ratios of most genes are within the range of 1.1 tot 1.2. Individually these alleles are dwarfs compared to the HLA giant. It should be noted that most of these identifications relate to SNPs around best matched candidate genes and for most cases the exact genetic variation involved still needs to be identified. Nevertheless one can already predict that most MS risk genes are linked to both adaptive and innate immune functions. This underscores the autoimmune character of the disease. Genes with presumed function in the central nervous system are under-represented. New generation genetics will help to pinpoint the exact functional variants involved and functional studies linking the genetic variants with immune activity are needed to explore how these genes exactly contribute to the pathogenesis of MS.