It is now widely accepted that the normal immune system harbors a regulatory T‐cell population specialized for immune suppression. It was found initially that some CD4⁺ T cells in normal animals were capable of suppressing autoimmunity. Characterization of this autoimmune‐suppressive CD4⁺ T cell population revealed that they constitutively expressed the CD25 molecule, which made it possible to distinguish them from other T cells, delineate their developmental pathways, in particular their thymic development, and characterize their potent in vivo and in vitro immunosuppressive activity. The marker also helped to identify human regulatory T cells with similar functional and phenotypic characteristics. Recent studies have shown that CD25⁺CD4⁺ regulatory T cells specifically express the transcription factor Foxp3. Genetic anomaly of Foxp3 causes autoimmune and inflammatory disease in rodents and humans through affecting the development and function of CD25⁺CD4⁺ regulatory T cells. These findings at the cellular and molecular levels altogether provide firm evidence for Foxp3⁺CD25⁺CD4⁺ regulatory T cells as an indispensable cellular constituent of the normal immune system and for their crucial roles in establishing and maintaining immunologic self‐tolerance and immune homeostasis. They can be exploited for clinical use to treat immunological diseases and control physiological and pathological immune responses.