Autoimmune diseases are frequently associated with the production of autoantibodies by cells that escaped the protective mechanisms that control self-tolerance. Some of these cells develop into long-lived plasma cells which are predominantly located in the bone marrow. The generation of this particular type of cell requires specific migration, differentiation, and survival signals. The identification of some of the factors involved in these pathways has permitted the development of specific therapeutic approaches and may even provide investigators with further new therapeutic targets, particularly in autoimmune diseases associated with persistent autoantibody production. We reviewed the existing evidence for the mechanisms implicated in the perpetuation of long-lived plasma cells and the most recent therapeutic proposals in this context. (C) 2011 Elsevier B.V. All rights reserved.