Immunological treatments of progressive multiple sclerosis are discussed. Recent trials of interferon-beta 1b(IFN beta-1b) and IFN beta-1a in secondary progressive MS (SPMS) have demonstrated treatment benefits on relapse rate and accumulation of MRI lesions, and one trial of IFN beta-1b showed significant slowing of disability progression. In another recent study, mitoxantrone, a potent immunosuppressive agent, was reported to reduce progression of disability in SPMS. As regards primary progressive MS, there is currently no convincing disease-modifying treatment. Pathologic studies have revealed that axonal injury is prominent in MS and may be the explanation for irreversible disability. It is hoped that therapeutic strategies will be aimed at axonal loss as well as inflammation and demyelination.