Regulation of the immune system is fundamental for proper immune function and homeostasis. In the periphery, regulatory T cells provide self-tolerance and protect the host from harmful autoreactive T cells. Regulatory T cells are also involved in the pathogenesis of chronic viral infectious diseases and cancer. Both the CD4(+) and the CD8(+) T cell compartments contain regulatory T cells. Although various CD4(+) regulatory T-cell subsets represent the best characterized regulatory T-cell populations, CD8(+) regulatory T cells also have strong immunosuppressive properties and are involved in the pathogenesis of various clinical conditions. In this review, we will discuss the phenotypic and functional characteristics of CD8(+) regulatory T cells in comparison to CD4(+) regulatory T cells.