Conventional treatment of autoimmune hemolytic anemia (AIHA) comprises corticosteroids and splenectomy and/or other immunosuppressive drugs for refractory/relapsed patients. Monoclonal antibodies (MoAbs) rituximab and alemtuzumab have gained widespread acceptance in the management of B-cell malignancies. More recently, they have been used to treat a number of autoantibody-mediated diseases, such as both idiopathic and secondary AIHA, with encouraging results. Herein we report an overview of the medical literature on the use of MoAbs to treat AIHA. The therapeutic mechanism of action of rituximab in the treatment of autoimmune diseases such as rheumatoid arthritis and lupus is currently a subject of considerable investigation. We have proposed that cell-associated IgG immune complexes, generated by the binding of rituximab to CD20 on B cells, may serve as decoys that attract FcγR-expressing effector cells and downregulate effector cell pathogenic action, thus reducing inflammation and tissue destruction in these diseases. We briefly review evidence that suggests that this immune complex decoy hypothesis plays a role in the therapeutic action of rituximab in AIHA, and we propose new measurements that should allow for a more complete evaluation of the importance of this mechanism in AIHA.