Multiple sclerosis (MS) is an inflammatory demyelinating disorder. Although all MS patients initially show a relapsing-remitting course, 20–50% subsequently enter a chronic progressive course at 10–20 years after onset that greatly influences their activities of daily living. There are 2.5 million MS patients worldwide with large regional and racial differences. In particular, there are many MS patients among Caucasians living in Europe, while the disease is relatively rare in Asians and Africans. Although MS is regarded as an autoimmune disease, many factors such as genetic background, environmental factors, and sex are involved in its pathogenesis. While the immunological mechanisms remain to be fully elucidated, invasion of autoreactive T cells into the central nervous system (CNS) tissue is considered the first step of the disease. These T cells react with myelin antigens and initiate demyelination of the CNS by activating cytotoxic T cells, macrophages, and B cells through the release of inflammatory cytokines. As a treatment option, disease-modifying therapies have recently been developed to prevent the recurrence of MS in addition to conventional treatment with corticosteroids for acute relapse. However, there are still few effective treatments for the chronic progressive phase, and it is thus imperative to decipher the mechanism for chronic progression.