Regulatory T (Treg) cells play central role in regulation of immune responses to self‐antigens, allergens, and commensal microbiota as well as immune responses to infectious agents and tumors. Transcriptional factor Foxp3 serves as a lineage specification factor of Treg cells. Paucity of Treg cells due to loss‐of‐function mutations of the Foxp3 gene is responsible for highly aggressive, fatal, systemic immune‐mediated inflammatory lesions in mice and humans. Recent studies of Foxp3 expression and function provided critical novel insights into biology of Treg cells and into cellular mechanisms of the immune homeostasis.