Mantle cell lymphoma (MCL) is generally considered incurable and has the worst overall survival among B-cell lymphoma subtypes. The disease usually responds well to initial therapy but most patients relapse and then respond only briefly to salvage therapy. Nevertheless, the median overall survival of MCL patients has dramatically improved from 2 to 3 years of the 90’s to more than 5 years at present. This improvement was due either to the introduction of dose-intensive strategies and/or high-dose therapy upfront in younger patients, and to the availability of novel agents in older patients or in the relapsed/refractory setting. Bendamustine, mostly in combination with rituximab, has been recently introduced in the armamentarium for treating patients with MCL with surprising results. Its efficacy and tolerability compare favorably with any other cytotoxic drug or drug combinations for treating patients with MCL, as summarized in this review. Due to its favorable toxicity profile, bendamustine is now increasingly combined with other active compounds. Cytosine arabinoside, which is well known for its striking activity in younger patients with MCL, has been combined with bendamustine in the rituximab, bendamustine and cytarabine (R-BAC) regimen with promising results. Other novel agents, that are approved in Europe or in the United States for the treatment of MCL, like bortezomib, lenalidomide, temsirolimus, and drugs targeting the B-cell receptor pathway (idelalisib, ibrutinib), are under investigation in combination with bendamustine. These molecules provide an opportunity to build up on the regimens used in MCL either in combination with bendamustine upfront, or as maintenance, and will open new frontiers in the treatment of patients with MCL.