While CD4⁺CD25^high regulatory T cells (Tregs) have garnered much attention for their role in the maintenance of immune homeostasis, recent findings have shown that subsets of CD8⁺ T cells (CD8⁺ Tregs) display immunoregulatory functions as well. Both CD4⁺ Tregs and CD8⁺ Tregs appear impaired in number and/or function in several autoimmune diseases and in experimental animal models of autoimmunity, suggesting the possibility of immunotherapeutic targeting of these cells for improved management of autoimmune conditions. Our group has developed a strategy to induce CD8⁺ Tregs in autoimmune mice through the use of a tolerogenic self-peptide, and new information has been gained on the phenotype, function and role of induced CD8⁺ Tregs in autoimmunity. Here we present an overview of the role and mechanisms of action of CD8⁺ Tregs in autoimmunity, with a special focus on lupus. We also discuss the potential role of CD8⁺ Tregs in other diseases, including chronic infection and cancer.