The treatment of HAM/TSP is a challenge. No agent has shown to significantly modify the long-term disability associated with HAM/TSP. Advances in our understanding of the pathogenesis of HAM/TSP have led to the identification of several biomarkers and therapeutic targets. Clinical trials in HAM/TSP continue to be opportunities for further qualification and refinement of biomarkers and therapeutic targets. The validation of HAM/TSP relevant biomarkers and the identification of new targets remain key challenges in the development of effective targeted therapy in HAM/TSP.