Autoimmune diseases such as systemic lupus erythemathodes (SLE) display quantitative and/or qualitative deficiencies of CD4+CD25+ regulatory T cells (Treg). This might contribute to the immune dysregulation and break-down of peripheral tolerance mechanisms. In addition novel subsets of Treg might arise under specific autoimmune conditions as an effort to counteract autoimmunity. Advances in our understanding of how to characterise and manipulate Treg in patients with autoimmune diseases are required in order to develop new therapeutic strategies.