Autoimmune hemolytic anemia (AIHA) is caused by the production of pathogenic antibodies that are directed against a patients own red cells, resulting in their destruction. The initial phase of AIHA is characterized by a loss of self-tolerance and the accumulation of multiple autoantibody specificities. Consistent with a role for T cells in providing help to B cells, autoantigens in AIHA are recognized by T-helper (Th) cells. Multiple factors may contribute to the stimulation of autoreactive Th cells, including inappropriately activated or aberrant antigen-presenting cells. In this session, we will review the pathophysiology of AIHA, discuss the origin and functional characteristics of the immune effectors that lead to red cell destruction and describe some of the immune effector control mechanisms that exist in healthy individuals but fail in AIHA. Information from this session is intended to help guide therapy to restore immune tolerance for this patient population.