Immunological tolerance involves maintaining a state of unresponsiveness to autoantigens while generating protective immunity against invading pathogens. Recently, a surprising resurgence in research on regulatory T cells has been noted, and few areas have enthralled immunologists and generated so many ardent debates. Naturally occurring CD4⁺CD25⁺ regulatory T cells have become the cornerstone T-cell population mediating peripheral tolerance to autoantigens, as well as regulation of T-cell responses directed at foreign antigens. However, several fundamental questions concerning CD4⁺CD25⁺ T cells remain unanswered. Here, we propose to critically re-evaluate some recent conclusions and provide a consensus overview.