Mantle cell lymphoma (MCL) is a B-cell neoplasm that comprises about 5 percent of all non-Hodgkin lymphoma (NHL) cases diagnosed yearly. It is characterized by distinct morphological, immunophenotypic, genetic and clinical features. MCL cells typically express CD5, CD43, CD19, CD 20 and an IgM or IgD immunoglobulin on the cell surface, although some CD5-negative cases have been reported. Translocation (11;14) is present in approximately 95% of MCL cases and confirms the diagnosis in the majority of patients. Several other genetic abnormalities are also relatively common in this disease. The number of abnormalities present increases with time and appears to correlate with resistance to conventional therapies. Clinically most patients will present at diagnosis with advanced stage disease (stage III or IV), and will require some form of therapy within the first year of diagnosis. The advent of more modern regimens, which typically include consolidation with autologous stem cell transplantation, have markedly improved response rates. Nevertheless, the disease remains incurable and the current estimate of survival is 5-10 years after diagnosis. New small molecule inhibitors that target specific proteins and/or pathways that are essential to the survival and proliferative advantage of the malignant cell are showing promise in clinical trials and may allow therapy to be tailored to the patient’s disease, including individual mutations. While the future appears bright for this once dismal disease, much work remains before this goal can be reached.