Regulatory T lymphocytes unequivocally play a major role in the maintenance of immunologic homeostasis. The first descriptions of regulatory T lymphocytes concerned CD8(+) cells, but this field was brought into discredit when some of its central tenets turned out to be erroneous. CD4(+) regulatory T cells took over and, with the help of newly developed molecular tools, rapidly were phenotypically and functionally characterized. We now know that these cells control a large variety of immune responses. However some observations of in vitro or in vivo immune regulation could not be explained with CD4(+) regulatory T cell activity and depended on the action of a variety of CD8(+) T cell populations. In recent years, substantial progress has been made in the phenotypic and functional characterization of CD8(+) regulatory T cells. These cells play a role in the control of intestinal immunity, immunopathology, and autoimmunity, as well as in immune privilege of the eye, in oral tolerance, and in prevention of graft-versus-host disease and graft-rejection. The suppressor effector mechanisms used by these cells are in part shared with CD4(+) regulatory T cells and in part unique to this population. We here review the current literature on naturally occurring and experimentally induced murine CD8(+) regulatory T-cell populations.