Mantle cell lymphoma is characterized by an aggressive clinical course and poor prognosis, with only few long-term survivors. Conventional chemotherapy has failed to substantially alter the natural course of the disease and remains a palliative approach. However, several randomized trials have recently clearly demonstrated the superiority of a combined immunochemotherapy containing the anti-CD20 antibody rituximab. In addition, a randomized trial has shown a significantly improved progression-free survival after myeloablative radiochemotherapy with autologous stem cell transplantation similar to other dose-intensified approaches (hyper-CVAD). Unfortunately, the vast majority of patients will eventually relapse. However, numerous molecular targeting strategies (e.g. proteasome inhibitors, immunomodulatory drugs or radiolabeled antibodies) have achieved promising results in early phase II studies.