Mantle cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphomas (NHL) characterized in almost all cases by the chromosomal translocation t(11;14)(q13;q32) and nuclear cyclin D1 overexpression. Most patients present with advanced stage disease, often with extranodal dissemination, and typically pursue an aggressive clinical course. Recent improvement has been achieved by the successful introduction of monoclonal antibodies and dose-intensified approaches including autologous stem cell transplantation strategies. However, with the exception of allogeneic hematopoietic stem cell transplantation, current treatment approaches are not curative and the corresponding survival curve is characterized by a relatively steep and continuous decline, with a median survival of about 4 years and <15% long-term survivors. Despite its rarity, MCL is of particular clinical and scientific interest by providing a paradigm for neoplasms with dysregulated control of cell cycle machinery and impaired apoptotic pathways. Recently gained insights into underlying pathobiology unravel numerous promising molecular targeting strategies, however their introduction into clinical practice and current treatment algorithms remains a challenge. This article will provide relevant information for decision making in clinical practice and give a perspective on upcoming management strategies.