Multiple sclerosis (MS) is thought to be an autoimmune disorder, mediated by myelin-specific T cells. Recent studies demonstrate that activated T cells specific for MBP are increased in MS, and that the MBP-specific T cells and T cell infiltrates in MS brains conserve homologous TCR CDR3 motifs. Since the CDR3 motifs are also shared by encephalitogenic T cells inducing EAE, it is likely that therapeutic strategies effective for EAE may be useful for MS. In this review, I discuss the possible application of TCR vaccination, TCR antagonist peptides and oral tolerization. Considering the chronic relapsing features of MS, treatments which are safe and may tighten the immune regulatory networks are recommendable.