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Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is chronic progressive myelopathy characterized by bilateral pyramidal tracts involvement with sphincteric disturbances. HTLV-I infects approximately 10-20 million people worldwide. There are large endemic areas in southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa. Since the primary neuropathological feature of HAM/TSP is chronic inflammation caused by HTLV-I infection in the spinal cord, various treatments focusing on immunomodulatory or anti-viral effects were performed for HAM/TSP patients until now. However, there are still many of problems, such as insufficient effects, side effects and expensive costs in long-term treatments, etc., in these treatments. Therefore, an ideal therapeutic strategy against HAM/TSP is still not established yet. Although only a small proportion of HTLV-I-infected individuals develops HAM/TSP, neurological symptoms are certainly progressive once myelopathy develops, leading to deterioration of the quality of life. Therefore, we now need the therapeutic regimens to protect the development, or be able to commence the treatments as soon as possible after the development safely and inexpensively even in long-term course or lifelong course of treatment. As HTLV-I-infected CD4(+) T cells are the first responders in the immunopathogenesis of HAM/TSP, the ideal treatment is the elimination of HTLV-I-infected cells from the peripheral blood. In this article, we will review the therapeutic strategies against HAM/TSP up to now and will introduce our new therapeutic approach focusing on the targeting of HTLV-I-infected cells in HAM/TSP patients.