© 2015, Nova Science Publishers, Inc. Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin’s Lymphoma (NHL) with varying clinical presentations, ranging from indolent disease to highly aggressive clinical course. The MCL cells exhibit a characteristic translocation t(11;14) which juxtaposes immunoglobulin heavy chain gene with gene for cyclin D1 leading to overexpression of cyclin D1 which can be identified by immunohistochemistry and is useful as a diagnostic marker. Advancement in understanding of the biology and pathogenesis of MCL has led to discovery of multiple other genetic alterations impacting the cell cycle deregulation and development of sub clonal populations with certain genetic mutations (p53, ATM, NOTCH2) leading to disease progression and refractoriness to treatment. Mantle cell lymphoma international prognostic index (MIPI) and biologic MIPI (bMIPI) are prognostic indices to categorize indolent vs aggressive disease. Currently an intensive cytarabine containing upfront induction regimen followed with or without autologous transplant is recommended for younger and fit patients. Older or frail patients are thought to benefit more from less intensive rituximab containing regimens followed by rituximab maintenance. A small subset of patients with indolent disease can be observed. Most patients unfortunately relapse. Targeted molecular therapies (bortezomib, lenalidomide, ibrutinib, idelalsib etc.) have shown significant response rates in relapsed and refractory disease and are being evaluated further.