Diffuse large cell B-cell lymphoma (DLBCL) is the most common lymphoma in the western world. The most common symptom is lymphadenopathy. General symptoms may include a decrease in performance status, loss of weight, fever and night sweats. DLBCL is treated with a combination of anthracyclin-based chemotherapy and the CD20 antibody rituximab. 70% of the patients can be cured with the combination therapy. To date, clinical risk factors remain as the cornerstone of treatment decisions and prognosis. Biological prognostic factors and targeted therapies are, however, under active research and it is likely that patients will in the near future be treated according to risk-adapted and biomarker-driven therapies.