Mantle cell lymphoma (MCL) is an uncommon subtype of B-cell lymphomathat is characterized by monoclonal B cells that express CD5 on their surface, but not CD23, and harbor the t(11:14) chromosomal translocation that leads to dysregulated expression of cyclin D1. MCL is a biologically and clinically heterogeneous disease. It has the unfavorable characteristics of both aggressive and indolent lymphoma in that MCL is not curable with current standard therapy, yet patients have a shorter survival compared with other indolent histology. MCL is incurable, yet more intensive therapy does lead to longer disease-free intervals; therefore, treatment must be designed to optimize survival while maintaining quality of life. Thus, therapy should be individualized based on both the clinical behavior of the lymphoma and the patient’s status. While there is no clear standard therapy that can be recommended for all patients, there may be an optimal choice for each patient. Knowledge of the expected clinical benefits and toxicities of various approaches will allow the physician and patient to appropriately select the therapy.