Patients with mantle cell lymphoma (MCL) have a particularly poor prognosis when treated with standard chemotherapy, with a median overall survival of only 3 years. These patients have therefore been considered for first-line treatment with more aggressive or experimental strategies, such as high-dose therapy (HDT) with autologous stem cell transplantation (ASCT). While high rates of clinical remission have been achieved with HDT/ASCT, this procedure alone is not believed to be curative and different treatment strategies are being developed to improve outcomes in this group of patients. Single-agent rituximab is active in both newly diagnosed and relapsed MCL and therefore the addition of rituximab to chemotherapy regimens and/or HDT/ASCT may enhance their efficacy. Outside the transplantation setting, rituximab plus chemotherapy has been shown to be highly active in MCL, and preliminary data from randomized trials suggest that the combination may yield superior results compared with chemotherapy alone. The addition of rituximab to transplantation protocols appears to be a very promising strategy for patients with MCL, given as an in vivo purge before HDT/ASCT and/or as posttransplant maintenance therapy. Two phase II clinical trials with rituximab given as an in vivo purge during stem cell mobilization and as posttransplant immunotherapy in patients with previously untreated MCL have generated very promising data. Rituximab is an important addition to cytotoxic therapy and with HDT/ASCT represents a highly active therapy that may be superior to conventional treatment or HDT/ASCT alone in MCL. Randomized prospective studies and longer follow-up are needed to determine whether these regimens can achieve longer survival or possibly cure in this disease.