The recognition of self is a normal function of the immune system. A dysregulation of the tight control of auto-reactive lymphocytes in physiological conditions sometimes leads to the development of auto-immune diseases. Several recent elements bring new insights in the functioning of the immune system. Thus, the discovery of BAFF and APRIL and their receptors allow us to better understand the homeostasis and activation of B lymphocytes. The description of a new helper lineage, characterized by the secretion of IL-17 modifies the etiologic scheme of auto-immune diseases. Lastly, regulatory T lymphocytes play a major role in controlling auto-reactive lymphocytes and may participate in the genesis of auto-immune diseases. The emergence of these new data enables us to better understand the pathological mechanisms of complex auto-immunes diseases. However, further studies are necessary in order to specify the role of each one of these factors. This will enable a better targeting of treatments in order to improve the management of patients.