Multiple CD8(+) suppressive T cell (Ts) subtypes are now recognized as essential regulators of the immune system that prevent autoimmunity through secretion of multiple cytokines and the subsequent inhibition of effector lymphocyte function. CD8(+) Ts are an exciting area of study because of the possible therapeutic implications of inducing suppressive cells that are able to subdue or anergize autoimmune manifestations. Current research in systemic lupus erythematosus (SLE), a disease in which most effective therapies are widely immunosuppressive, is often focused on novel and highly targeted ways in which to treat this multiorgan disease. CD8(+) Ts have been impaired in human and murine SLE. Our group and others have utilized tolerogenic peptides to induce and study CD8(+) Ts to understand their function, as well as investigate a possible new SLE therapy. This review will discuss the similarities and differences in CD8(+) Ts subsets, the concept of tolerance as a therapy, and the current understanding of CD8(+) Ts in mouse SLE models.