Human T-cell leukemia virus type 1 (HTLV-1), also known as human T-lymphotropic virus type 1, causes the aggressive malignancy known as adult T-cell leukemia/lymphoma (ATL) in 5% of infected people and a chronic progressive inflammatory disease of the central nervous system, HTLV-1–associated myelopathy, in ∼0.3% to 4% of them, varying between regions where it is endemic. Reliable treatments are lacking for both conditions, although there have been promising recent advances in the prevention and treatment of ATL. Because ATL typically develops after several decades of infection, it is necessary to understand how the virus persists in the host despite a strong immune response, and how this persistence results in oncogenesis.