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Bendamustine is a uniquely structuredalkylating agent that lacks cross-resistance with other alkylators. This agent has a high degreeof activity against a variety of tumor cell lines.Based on clinical data from randomized phase III trials, bendamustine, with or without rituximab, hasbeen shown to be an appropriate option for first-line treatment or treatment of relapsed/refractory patients with indolent non-Hodgkin’s lymphoma or elderly patients with mantle cell lymphoma. Bendamustine treatment is associated with abetter therapeutic index and offers an improved overall quality of life compared to R-CHOP or R-CVP. It is now often used as achemotherapy backbone for combination with novel drugs including ibrutinib or idelalisib. This article provides a comprehensivesummaryof the clinical data along with practical adviceonhowto optimallymanagepatients with bendamustine therapy, includingdose recommendations, antiemetic prophylaxis, prevention of infusion and skin reactions, as well as prophylaxis of opportunisticinfections. This information might be helpful for clinicians using bendamustine in their daily practice.