Bendamustine (Treanda, Ribomustin) is a water-soluble, bifunctional chemotherapeutic agent that also has potential antimetabolite properties and only partial cross-resistance with other alkylators. Designed in 1963 and re-discovered in 1990s, this drug's unique mechanism of action and favorable side-effect profile promise a major role in the management of lymphoproliferative disorders. Bendamustine has been designated as an orphan drug in the United States, conferring prolonged market exclusivity. This article provides a comprehensive review of the data on efficacy and toxicity from trials investigating the use of bendamustine for the treatment of lymphoproliferative neoplasms. The pharmacology, pharmacokinetics, and pre-clinical studies with bendamustine are also reviewed. MEDLINE and Pubmed databases (1970-2010) were searched using the terms bendamustine, bendamustin, Treanda, Ribomustin, SDX-105, IMET-3393, and Cytostasan. All relevant articles were reviewed and references screened for additional articles. The databases of the American Society of Hematology (2004-2009) and the American Society of Clinical Oncology (1995-2009) were also searched for relevant abstracts. Bendamustine induces a remission in more than three-fourths of patients with rituximab-refractory indolent B cell non-Hodgkin lymphoma (NHL). Combined with rituximab in vitro, bendamustine shows synergistic effects against various leukemia and lymphoma cell lines. Clinical trials supporting these results show that bendamustine plus rituximab is highly effective in patients with relapsed-refractory indolent lymphoma, inducing remissions in 90% or more and a median progression-free survival of 23-24 months. Bendamustine has been reasonably well tolerated in clinical trials with low propensity to induce alopecia. Combination of bendamustine and rituximab has the potential to become a new standard first-line treatment option for patients with FL, MCL, and indolent lymphomas. Results of ongoing trials will help to further elucidate the optimal role of bendamustine in indolent NHL.