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Mantle Cell Lymphoma is a rare B-cell malignancy that can invade almost any structure in the body and recur after short-lived clinical responses. The pathogenesis and clinical features are well defined, but management has not yet been optimized. Induction with traditional immune-chemotherapy regimens that are used in other non- Hodgkin lymphomas rarely generate durable remissions. Therefore, clinical research is needed to improve treatment of de novo disease and to establish safe and effective regimens for maintenance and salvage options for relapsed or refractory disease. This comprehensive review discusses disease pathogenesis and focuses on emerging treatment paradigms using novel targeted therapies.