Increasing evidence suggests that rituximab added to salvage chemotherapy improves response rates and outcomes in relapsed DLBCL. In a recent randomized phase 3 study, the efficacy of adding rituximab to the DHAP-VIM-DHAP regimen was tested in 239 rituximab-naïve patients with relapsed or primary refractory aggressive cluster of differentiation 20 (CD20)+ B-cell NHL. In 225 evaluable patients, the addition of rituximab to second-line chemotherapy resulted in a significant improvement of ORR (75% versus 54%, p=.01) and PFS (52% versus 31% at two years, p<.002). Other small phase II trials (with a range of 35-55 patients) investigating rituximab in combination with ICE, DHAP or EPOCH have also shown encouraging results. However, the patients in these studies had not been previously exposed to rituximab, while at present, almost all patients with aggressive B-cell NHL receive rituximab combined with first-line chemotherapy.