Purpose of reviewPatients with relapsing mantle cell lymphoma (MCL) still represent a demanding challenge for the hematooncologist. The dismal prognosis and the absence of generally accepted therapeutic standards hamper the clinical management of such cases. Moreover, the availability of many targeted approaches, in a field so far missing efficient salvage regimens, challenges current therapeutic algorithms in these patients.Recent findingsMolecular targeted drugs provide unprecedented response rates in relapsed and even chemorefractory MCL. Many phase II studies demonstrated impressive antilymphoma activity of compounds such as bortezomib, lenalidomide and temsirolimus, whereas ongoing phase III trials currently assess the real world' benefit and the impact on survival, both alone and in combination with chemotherapy or monoclonal antibodies. Recently, the Bruton's tyrosine kinase inhibitor ibrutinib, targeting the B-cell receptor cascade, showed impressive response rates and will be soon available in phase III trials.SummaryIn the present review we focus on the major therapeutic discoveries of the last few years to offer a practical algorithm to select the appropriate treatment in patients with relapsed MCL.