Mantle cell lymphoma is molecularly characterized by the chromosomal translocation t(11;14) (q13;q32) that results in a constitutional overexpression of the cell cycle regulator protein cyclin D1. Generally, the disease is characterized by rapid relapses and poor long-term outcome. However, a subset of patients with indolent disease has been identified. Randomized trials have demonstrated the superiority of dose intensified, cytarabine-containing induction with or without autologous stem cell transplantation in younger patients. In elderly patients, a rituximab-based maintenance has significantly prolonged progression-free and overall survival after treatment with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP). Unfortunately, the vast majority of patients will eventually relapse. Numerous molecular targeting strategies (bortezomib, lenalidomide, temsirolimus, and especially inhibitors of the B-cell receptor pathway) have achieved high response rates in phase II studies and should be strongly considered in relapsed disease.