Over the twenty-five years since the association of human T-cell lymphotropic virus type 1 infection with tropical spastic paraparesis, little progress has been made in the treatment of this chronic debilitating condition. The purpose of this review is to highlight the most informative results and to identify the most promising candidates for further study. Although many small observational studies have been reported, only twice have the positive data been tested in randomized controlled studies. In the first study, interferon-alpha 3 MU was found to be better than 0.3 or 1 MU over four weeks, whilst zidovudine plus lamivudine performed no better than placebo after 24-48 weeks of therapy in the second study. Preliminary data from studies of immunomodulatory therapy including cyclosporine and monoclonal antibodies to CD25 and interleukin-15 are encouraging and further comparative studies are indicated with the combination of antiretroviral therapy with histone deacetylation inhibition, which has been shown to reduce simian T-lymphotropic virus type 1 proviral load in baboons, unless this proves unsuccessful in human T-cell lymphotropic virus type 1 infection.