FoxP3 recently entered the spotlight as a critical component of regulatory T cell development and function. Several groups are presently engaged in an effort to uncover the mechanistic details of its contribution to this critical T cell subset. Despite this, the mechanism of FoxP3-mediated transcriptional repression and the affected target genes are still largely unknown. First, we discuss insights from work on other Fox family members with an emphasis on those with known roles in the immune system. Second, we review recent data concerning the molecular mechanism of FoxP3 function and its role in human disease. Finally, we consider what is known about FoxP3 target genes and their effect on T cell physiology.