Autoimmune hematological disorders encompass a broad group of hematological conditions characterized by the loss of self-tolerance to a variety of antigens. Despite good response to first-line therapy in the majority of patients, relapses are common, necessitating new and safe therapeutic options. The anti-CD20 monoclonal antibody rituximab has led to substantial improvement in the treatment of malignant and immune-mediated disorders involving B cells. Although experience with rituximab in immune-mediated hematological disorders is rarely supported by randomized trials, there is now substantial experience with rituximab suggesting that anti-CD20 therapy is an effective and well-tolerated alternative to immunosuppressive therapy in these disorders. However, caution is needed based on recent reports describing—sometimes severe—rituximab-related complications. Am. J. Hematol. 2011. © 2011 Wiley-Liss, Inc.