Rituximab, a chimeric anti-CD20 IgG1 monoclonal antibody, is an innovative drug that confers significant survival improvements in both indolent and aggressive B-cell non-Hodgkin lymphomas (B-NHL) when combined with chemotherapy such as CHOP (R-CHOP) regimen in several phase III trials. Rituximab also has potent anti-tumor activity when used as a single agent in indolent B-NHL. However, many patients with B-NHL tend to relapse or eventually become refractory to rituximab treatment, either alone or in combination with chemotherapy. Especially, indolent B-NHLs are hard to cure. To further improve the efficacy of initial therapy for indolent B-NHL, several worldwide phase III trials have been conducted. First, Japan Clinical Oncology Group evaluated dose-dense strategy of R-CHOP-14 with G-CSF (Watanabe T, et al. J Clin Oncol 2011). Second, the role of upfront radioimmunotherapy was evaluated by European (Morschhauser F, et al. J Clin Oncol 2008) and US Intergroup (Press OW, et al. ASH 2011) trials. Third, the impact of maintenance rituximab following R-alone for low tumor burden (Kahl BS, et al. ASH 2011) or R-chemotherapy for high tumor burden (Salles G, et al. Lancet 2011) was assessed. Fourth, R-bendamustine was compared with R-CHOP in German study (Rummel MJ, et al. ASH 2009). Finally, several studies evaluating the safety and efficacy of novel monoclonal antibodies are being conducted. On the other hand, for aggressive B-NHL with high intermediate or high risk of International Prognostic Index, (R-)CHOP followed by autologous stem cell transplantation with high dose therapy was compared with (R-) CHOP-alone in a phase III trial coordinated by the Southwest Oncology Group (Stiff PJ, et al. ASCO 2011). Results of these trials will be presented during the meeting, and we want to discuss the future direction of clinical trials to improve outcome of B-NHL patients.