Mantle cell lymphoma is a rare subtype of B-cell Non-Hodgkin-lymphoma which is clinically characterized by its heterogeneous behaviour with courses ranging from indolent to highly aggressive cases with limited prognosis. Targeted treatment alternatives in first-line and relapse settings are more and more shaping the therapeutic landscape of MCL. The development and implementation of new targeted and immunotherapeutic approaches have already improved outcomes for MCL patients with refractory or relapsed disease. However, long-term prognosis is still limited and patients with relapsed/refractory disease, especially those failing BTK inhibitor treatment, usually have a dismal outcome. This review summarizes the current and emerging treatment options for relapsed/refractory mantle cell lymphoma, focusing on the implementation of combined targeted treatment strategies such as BTK inhibitors and BCL2 inhibitors as well as immune-therapeutic approaches including CART-cells and bispecific antibodies.