The clinical course of patients with B-cell chronic lymphocytic leukemia (CLL) is often made complicated by autoimmune phenomena which mainly target the blood cells. Among them, the autoimmune hemolytic anemia (AIHA) is the most common form. On the other hand, it is believed that CLL is the most common of the known causes of AIHA. The source of any putative autoantibody (bystander nonmalignant cells or tumor cells) is not clear yet. Recently, it has been hypothesized that leukemic B-cells may also act as professional antigen presenting cells (APCs). With respect to the management of CLL-associated AIHA, steroids still represent the first-line treatment option. Intravenous immunoglobulin, immunosuppressive drugs, and splenectomy are also frequently used for steroid-refractory forms. Furthermore, although the case series is still too small, encouraging data is now supporting the use of monoclonal antibodies, in particular anti-CD20 rituximab, in managing this often life-threatening autoimmune complication of CLL.