Regulatory T cells (T(reg) cells) play an important role in the regulation and suppression of immune responses to self- and foreign antigens. Suppressed and impaired host immune responses are a major characteristic of many persistent human virus infections, such as those caused by human immunodeficiency virus (HIV), hepatitis C virus (HCV), and herpes virus. It has recently become evident that immune regulation mediated by T(reg) cells may comprise one mechanism that contributes to the impairment of virus-specific immune responses. Indeed, during viral infection, the generation of distinct subsets of CD4+ as well as CD8+ T(reg) cells has been reported. The phenotypic and functional heterogeneity of T(reg) cell subsets involved in the suppression of virus-specific immune responses suggests that different mechanisms and factors contribute to the generation of those cells during viral infection. This review focuses on the CD8+ T(reg) cell subset and summarizes current knowledge about the induction and function of CD8+ T(reg) cells in persistent human virus infections.