Juvenile idiopathic arthritis (JIA) is in a majority of the cases of self-limiting, and sometimes even a self-remitting, disease. A growing amount of data suggests that active T cell regulation determines, at least partly, the clinical outcome of JIA. In experimental models of arthritis, a group of highly conserved microbial proteins, heat shock proteins (hsps), can be used to effectively prevent and treat arthritis. This protection is mediated through the induction of cross-reactive T cell responses to self-hsps. In JIA, naturally occurring T cell immune responses to hsps are associated with disease remission in restricted oligoarticular JIA. Moreover, those responses are associated with the induction of T cells with a regulatory phenotype. Taken together, these data imply that immune modulation with hsps can be an effective way to restore natural occurring T cell responses, and, thus, treat JIA and rheumatoid arthritis.