While some improvement was achieved by adding etoposide and shortening the treatment intervals from 3 to 2 weeks (CHOEP-14), best results in young good-prognosis patients (age-adjusted International Prognostic Index [IPI] = 0,1) have been achieved with six cycles of CHOP (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone)-like chemotherapy in combination with the anti-CD20 antibody rituximab (Rituxan). The role of additional radiotherapy in this setting remains to be determined. With this approach, 2-year event-free survival rates of > 90% and overall survival of > 95% can be achieved in a very favorable subgroup (patients without IPI risk factor and no bulky disease), while further improvement is warranted for the less favorable subgroup (event-free survival only 77%). For young poor-prognosis patients (age-adjusted IPI > or = 2), the 5-year survival is around 50%, and progress has not been convincingly and specifically demonstrated in these patients. Ongoing studies will show whether dose-dense conventional or high-dose chemotherapy regimens requiring stem cell support in combination with rituximab will result in similar improvements of outcome as has been reported recently for young patients with good-prognosis aggressive lymphoma. In elderly patients, CHOP interval reduction from 3 to 2 weeks (CHOP-14) and the addition of rituximab to CHOP-21 achieved similar improvements in outcome. The ongoing RICOVER-60 (rituximab with CHOP over 60) trial of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL) evaluates whether the combination of both approaches (R-CHOP-14) can further improve the prognosis of elderly patients.