Rituximab plays an important role in the treatment of non-Hodgkin lymphoma (NHL). In spite of high response rates achieved with this monoclonal antibody, however, many patients with NHL tend to relapse and become refractory to rituximab over time. At the 2009 meeting of the American Society of Hematology (ASH), researchers presented results from several new approaches that may provide a boost to the NHL treatment armamentarium.Important long-term safety data were presented for bendamustine, a bifunctional alkylating agent that was approved by the US Food and Drug Administration in 2008 for chronic lymphocytic leukemia and indolent B-cell NHL that is resistant to rituximab. In addition, emerging evidence concerning the combination of bendamustine, rituximab, and bortezomib was presented. Other trials discussed the use of novel monoclonal antibodies such as of atumumab, GA101, PRO131921, and inotuzumab ozogamicin, which are directed at new biological targets for the treatment of NHL. Researchers also discussed recent trials of lenalidomide, an oral immunomodulator, alone and in combination with rituximab. Other novel agents discussed at the ASH meeting included clofarabine and CAL-101.