The Transcription factor FoxP3 belongs to the forkhead/winged-helix family of transcriptional regulators and shares general structural features with other FoxP family members. FoxP3 functions as a master of transcription for the development of regulatory T-cells (Treg cells) both in humans and in mice. Natural genetic mutations ofFoxP3 that disrupt its function in humans result in an autoimmune syndrome called Immune Polyendocrinopathy, Enteropathy, X-linked (IPEX) and in mice, its deletion causes the Scurfy phenotype, with similar pathology. The finding that FoxP3 is required for the development and function of Tregs has led to an explosion of research in determining its regulation and function in the immune system. Understanding the biological properties of FoxP3 has a wide range of implications for immune tolerance, autoimmune disorders, inflammation and immune response to infectious diseases and cancer.