Mantle cell lymphoma is an aggressive and rare type of non-Hodgkin’s lymphoma that is considered incurable. It is a heterogeneous disease with diverse clinical presentations and complex treatment courses. In this chapter, the presentation, diagnosis, and conventional treatment will be discussed and outlined for the frontline setting in both young fit adults and the elderly. This will be followed by an in-depth analysis regarding exciting novel therapies and combinations being investigated, from early stage development to ongoing clinical trials. We will finish with a recommended treatment algorithm for frontline and relapsed disease.