This chapter discusses the viral models and models that involve in the treatment of experimental autoimmune encephalomyelitis (EAE) by viral gene therapy. Three strains of Theiler's virus have been studied: the GDVII, Daniel (DA), and BeAn strains. Initial studies of the determination of virulence by Semliki Forest virus (SFV) involved in generation of mutants of the virulent L10 strain. In its pathogenicity in mice, JHM coronavirus shows similarities to Theiler's virus and SFV. The three models have similarities to MS. For all three models, virulent and avirulent forms of the virus are available, but demyelinating disease is induced in all cases by the avirulent form. Modification of the possible pathogenicity of viruses and their use to treat disease rather than cause it is the basis of viral gene therapy. For MS this has so far been attempted in pre-clinical experiments using an animal model of MS in mice, EAE.