It has been 65 years since the scurfy mutation arose spontaneously in mice at the Oak Ridge National Laboratory in the United States, and it is 13 years since the molecular cloning of the forkhead box P3 (FOXP3) gene was reported. In this Timeline article, we review the events that have occurred during and since this time. This is not meant as an exhaustive review of the biology of FOXP3 or of regulatory T cells, rather it is an attempt to highlight the landmark events that have demonstrated the importance of FOXP3 in immune function. These events have driven, and continue to drive, the extensive research effort to fully understand the role of regulatory T cells in the immune system.