During the last few years, new insights into the biology of mantle cell lymphoma have been obtained. However, with a median survival of only 3 years, mantle cell lymphoma remains the lymphoma subtype with the poorest prognosis. At initial diagnosis most patients present with advanced Ann Arbor stage III or IV and conventional chemotherapy hardly alters the continuously declining survival curve. Recently, two prospective randomized studies of the German Low Grade Lymphoma Study Group (GLSG) clearly confirmed the superiority of a combined immunochemotherapy. In a randomized study of the European mantle cell lymphoma Network, consolidation with myeloablative radiochemotherapy followed by autologous stem cell transplantation improved the progression-free survival in patients younger than 65 years. However, relapses are still observed at a high frequency. Thus, new therapeutic strategies such as radioactively labeled antibodies or molecular targeting agents (e.g. Bortezomib or flavopiridol) are urgently warranted to further improve the clinical outcome of mantle cell lymphoma.