Mantle cell lymphoma (MCL) is a rare and incurable subtype of non-Hodgkin's lymphoma that generally affects older individuals. However, the use of high-dose therapy and autologous stem cell transplant has improved significantly the prognosis of this hematological malignancy, but at the cost of increased toxicities, such as acute toxic death and secondary malignancies. But thanks to a rising understanding of the biology of MCL, the explosion of specifically targeted new efficacious agents, immunotherapy agents, and cellular therapies in the frontline setting, the prognosis of MCL is expected to improve dramatically.The initial treatment of MCL is currently not standardized and the therapeutic landscape of MCL is rapidly evolving. This review provides an extensive overview of the current frontline therapy trials for MCL and presents the results of innovative regimen, including some integrating novel agents and desintensified chemotherapy.