Adult T cell leukaemia / lymphoma (ATLL) is a mature (post thymic) T cell lymphoma caused by the human T-lymphotropic virus type 1 (HTLV-1) infection. Overall survival in the aggressive subtypes (Acute Leukaemia and Lymphomatous) remains poor in part due to chemotherapy resistance. To improve treatment outcome for de novo disease, better induction therapies are required and since the pathogenic agent is known it would seem sensible to target the virus. In a recent meta-analysis the use of zidovudine and interferon alpha (ZDV/IFN) has been associated with improved response rates and prolonged overall survival in leukemic subtypes of ATLL (both acute and Chronic) confirmed in a multivariate analysis. In a more recent UK study the overall response rate for patients with aggressive ATLL treated with chemotherapy alone was 49 % compared to 81 % with combined first line therapy (chemotherapy with concurrent or sequential ZDV/IFN). Combined first line therapy prolonged median OS in acute (p = 0.0081) and lymphomatous ATLL (p = 0.001).These data support the use of low dose ZDV/IFN with chemotherapy as first line treatment for patients with newly diagnosed aggressive ATLL. Although the mechanisms of action are incompletely understood, some possible explanations for their efficacy will be discussed.