Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that is the causative agent of a progressive neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic neuroinflammatory disease characterized by spastic paraparesis, lower limb sensory disturbance and bladder/bowel dysfunction. Over the twenty-five years since the discovery of this disease, significant advancements have been made in the pathogenic mechanisms associated with HAM/TSP, however, little progress has been made in the treatment of this disorder. This review highlights the natural history of HAM/TSP, informative results of clinical trials, and discusses the current and future approaches to the treatment of HAM/TSP within the context of our understanding of the underlying pathogenic mechanisms.