Journal of Clinical Oncology A large number of frontline treatment options exist for mantle cell lymphoma (MCL), making selection of therapy a challenge for the clinician. In this Oncology Grand Rounds article, the case of a 73-year-old woman with MCL who attained remission with bendamustine and rituximab is presented. The relevant literature regarding frontline therapy is then reviewed, with particular focus on selection of induction regimen and the potential roles for autologous transplantation and/or rituximab maintenance. This literature primarily consists of prospective phase 2 and phase 3 clinical trials; however, added to this literature now is a growing body of large retrospective real-world cohorts, such as the new analysis by Martin et al, the manuscript that accompanies this Oncology Grand Rounds article. In some cases, the real-world evidence is at odds with data from prospective clinical trials, such as regarding the role of rituximab maintenance after bendamustine plus rituximab induction. These important new real-world data are put into context of an ever-changing treatment landscape, in hopes of aiding clinicians in frontline treatment selection for patients with MCL.