Rheumatoid Arthritis (RA) is one of the three diseases most commonly seen in rheumatology consultation being cause of a great demand in health care services globally. Its etiology remains unknown, and although attempts have been made to recognize the target auto-antigens, it is still unknown. The immune response of these patients is characterized by the involvement of multiple cells and effectors molecular inflammatory mechanisms. However, from this complex view emer- ges a common point, it is, the escape of the mechanisms of immune control. Understanding of reason and sense of loss of tolerance, the activation of auto-reactive T cells and the generation of auto antibodies is fundamental to understand the physiopathology of rheumatoid arthritis and develop specific immune-therapeutic strategies.