Multiple sclerosis (MS), typically considered a disease of young adults, is increasingly recognized in early-onset pediatric cases (PMS), with an estimated 3%-5% of patients having onset before age 16 years. Given its rarity, it is challenging to investigate the mechanisms that initiate MS in such young individuals and to assess whether PMS and adult MS share the same risk factors, rather than being 2 separate conditions. Population-based studies investigating the familial aggregation of MS clearly showed genes play a role in adult MS. Most of this genetic risk is mediated by specific risk alleles in the major histocompatibility complex (MHC) class II region. However, genome-wide association studies (GWAS) have provided evidence for more than 50 single nucleotide polymorphisms (SNPs) of more modest effect that also influence the risk of adult MS.