The recent characterization of a mutant strain of mice generated five decades ago in a program to study ionizing radiation in mammals (and, ironically, derived from a nonmutagenized control animal) is helping to dissect a now resurgent area of immunology. Despite a vast literature during the 1970s, the study of suppressor T cells had been largely abandoned until the publication of several seminal papers rekindled interest in what are today generally referred to as regulatory T (T_R) cells. The identification of the transcription factor Foxp3 as the gene responsible for the defect in scurfy mice, and subsequently, the demonstration of its critical involvement in the generation of T_R cells, provides an important molecular insight into this essential cell lineage.