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A rare tumor, primary central nervous system lymphoma can affect immunocompetent and immunocompromised patients. While sensitive to radiotherapy or chemotherapy crossing the blood-brain barrier, it often recurs. Modern treatment consists of high-dose methotrexate-based induction chemotherapy, often followed by consolidation with either radiotherapy or further chemotherapy. Neurotoxicity is however a concern with radiotherapy, especially for patients older than 60 years. The benefit of the addition of rituximab to chemotherapy is unclear. Targeted therapies and immunotherapy have been effective in some patients and are tested on a larger scale. Survival has improved in the last decade, but remains poor in older patients.