Enormous progress has been made in the treatment of diffuse large B-cell lymphoma (DLBCL), mostly due to the anti-CD20 antibody rituximab. More than 50% of elderly DLBCL patients can be expected to be cured by modern immunochemotherapy. The standard chemotherapy partner of rituximab is the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen. Elderly patients need particular attention and thorough evaluation if they are suited for the standard treatment or if they are candidates for palliative treatment. Rigorous supportive care including anti-infectious prophylaxis and growth factor support are mandatory. Whether there is still a role of additive radiotherapy in the R-CHOP era is under debate. While further intensification of chemotherapy might hardly be feasible in elderly patients, dose and schedule of rituximab appear to be optimizable. Patients failing after R-CHOP are a particular challenge as are frail patients who are not fit enough for R-CHOP. Further progress can be expected from novel antibodies and small molecules that interfere with signal transduction pathways essential for the survival of the lymphoma cell. To achieve this goal, prospective trials with large numbers of patients are necessary for which the continuous commitment of patients and physicians is indispensable.