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Diffuse large B-cell lymphoma is an aggressive non-Hodgkin lymphoma subtype which requires immediate treatment. Standard treatment is usually a combined immune chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Since R-CHOP was approved, several attempts to combine it with novel agents and/or use them as maintenance therapy failed to improve the outcome. Recently, maintenance with lenalidomide after standard immune chemotherapy showed promising results. This review discusses the most pertinent published and running studies, analyzing study design, results, and practicality.