Autoimmune complications are common in chronic lymphocytic leukemia (CLL), occurring in up to a quarter of all patients during the course of the illness. By far the most common manifestation is autoimmune hemolytic anemia (AIHA), followed by immune thrombocytopenia (ITP). It is not true to say that autoimmunity is confined to the formed elements of the blood since conditions such as paraneoplastic pemphigus and acquired angioedema do occur in CLL, but nonhematologic autoimmunity is very rare indeed. The pathogenesis of autoimmunity in CLL is unknown. It may be related to the ability of the CLL cells to act as antigen-presenting cells (APCs), and to process antigen (particularly the Rh protein) so as to reveal cryptic peptides that are seen as foreign by helper T cells. It is likely that a failure of regulatory T-cell function is also involved. Autoimmune episodes may be triggered by treatment, particularly with purine analogues. Such episodes are often severe and may be fatal. Treatment of CLL-associated autoimmunity follows conventional protocols, but non-response to primary treatments is not uncommon. Promising results have been obtained with cyclosporine and rituximab.