Auto-immune diseases (AID) represent an heterogeneous group of chronic inflammatory diseases which do not seem to result from the direct pathogenic effect of microorganisms or xenobiotics. Some AID are associated with the production of autoantibodies which, in some patients, may be involved in the development of tissue damages. In other AID, as in most experimental models of AID, T cells are responsible for the generation of tissue lesions by their cytotoxic activity or by the synthesis of cytokines. Mechanisms by which T and B cells are educated to tolerate self antigens are numerous and operate both in central lymphoid organs (thymus, fetal liver, bone marrow) and at the periphery. They imply either the destruction of autoreactive lymphocytes (clonal deletion) or their inactivation (clonal anergy). Recent advances in analyzing the mechanisms of autoimmunity have opened new therapeutical possibilities which are evaluated in spontaneous and experimental animal models of AID. Among the most promising approaches are the intervention on the cytokine network, T cell and peptide vaccination, oral tolerance and non depleting monoclonal antibodies.