The interplay between Tax and the DDR pathway dictates cell fate. In the early steps of HTLV-1 infection, Tax expression fuels unrestrained cells proliferation leading to DNA damage and engagement of the DDR pathway. Severity of genomic lesions determines the outcome of DDR activation: a transient cell cycle arrest allowing DNA repair and cell survival. If the damage cannot be repaired, cells undergo senescence or apoptosis. An intact DDR barrier would thus protect against malignancy. Checkpoint adaptation permits DNA damaged cells to proliferate, accumulate and fix mutations that can have detrimental, neutral, or positive effects on cell growth. Acquisition of growth-promoting mutations is the seed for ATL development, particularly when mutations abrogate the dependence on continued Tax-expression for growth. In this case, cells would indeed evade both DDR and immune response control.