The incidence of primary CNS lymphoma (PCNSL), which has considerably increased these last years, remains stable in the immunocompetent population, while it is steadily decreasing in the immunosuppressed population. The addition of high dose methotrexate (MTX) based chemotherapy (CT) before whole brain radiotherapy (WBRT) has clearly improved the prognosis of PCNSL with a median survival of three to four years. About 30% of the patients may hope to have a long survival and to be cured. In the elderly (age over 60 years) CT alone (without RT) is recommended as initial treatment. This approach seems useful to avoid RT and to reduce the risk of delayed neurotoxicity due to the combined treatment. In the young population (age less than 60 years), intensive chemotherapy followed by hematopoietic stem cell rescue (ICH) appears as a promising approach in recurrent tumors and potentially as an alternative option to RT as consolidation treatment in newly diagnosed patients. A prospective trial will be activated in France soon randomizing ICH and RT in the initial treatment of PCNSL.