Despite their first recognition almost 40 years ago, CD8(+) 'suppressor' T cells remain poorly characterized. Recent studies of these lymphocytes, now popularly referred to as regulatory CD8(+) T cells (CD8(+) Tregs), have helped clarify their important role in the regulation of autoimmune disease. Here, we review progress related to the identification, phenotype and function of CD8(+) Tregs. We also focus on a newly described subset, CD8alphaalpha(+)TCRalphabeta(+) Tregs, which in mice recognize a T-cell receptor-derived peptide in the context of the class Ib major histocompatibility complex molecule Qa-1. These Tregs target only activated T cells and complement the suppression provided by CD4(+)Foxp3(+) Tregs. Investigations leading to the detailed identification, expansion, maintenance and function of CD8alphaalpha(+) Tregs should result in new therapeutic strategies for human inflammatory diseases.