Adult T-cell leukemia/lymphoma (ATL) is the first human malignancy associated with a retroviral infection and occurs in approximately 5 % of the 15 million to 20 million people infected by human T-cell lymphotropic virus 1. In general, ATL is resistant to chemotherapy, and while awaiting new therapeutics, patients commonly face a detrimental progress of the disease and death. The viral oncoprotein Tax is a key player in the cause of ATL and acts by interfering with DNA repair, cell cycle, apoptosis, and proliferative cellular programs. The Shimoyama classification describes four different subtypes (acute, lymphoma, chronic, and smoldering) associated with different outcomes, and that require different treatment strategies tailored to the clinical presentation. In aggressive ATL (acute and lymphoma subtypes), clinical trials, mostly from Japan, have demonstrated that combinations of chemotherapy can induce acceptable response rates, especially in the lymphoma subtype. However, the overall outcome remains extremely poor owing to a high rate of relapse. Similarly, the so-called indolent forms (smoldering and chronic subtypes) have a poor outcome whether they are managed with watching and waiting or treated with chemotherapy. We recently realized a worldwide meta-analysis and showed that the combination of zidovudine and interferon alpha is highly effective in the leukemic subtypes of ATL and should be considered as standard first-line therapy in that setting. This combination has changed the natural history of the disease through achievement of significantly improved long-term survival in patients with smoldering and chronic ATL as well as a subset of patients with acute ATL. Patients with lymphoma-type ATL still benefit from chemotherapy induction with concurrent or sequential antiretroviral therapy with zidovudine and interferon alpha. Allogeneic stem cell transplantation is a promising option but has several barriers. New drugs such as the new antibody anti-CXCR4 show promising results. Prospective trials testing maintenance therapy in order to avoid relapse are warranted when the patient cannot undergo allogeneic stem cell transplantation.