The immune system is not only well equipped to control infections but also tightly controlled to prevent autoimmune disease. Despite the negative selection of T-cell clones in the thymus, mature T cells capable of recognizing self-antigens are present in every individual. Several types of specialized regulatory cells maintain homeostasis and prevent expansion of autoreactive T cells. In this issue of Immunological Reviews, the role of CD4+ regulatory T cells is extensively discussed. Suppression of T-cell responses by CD8+ T cells has received less attention. Here, we review research on Qa-1-restricted CD8+ regulatory T cells. We focus on the role of this class Ib major histocompatibility complex (MHC) molecule in both CD8+ regulatory T-cell activity and protection of activated T cells.