It is more than a decade since the discovery of the first forkhead-box (FOX) transcription factor in the fruit fly Drosophila melanogaster. In the intervening time, there has been an explosion in the identification and characterization of members of this family of proteins. Importantly, in the past few years, it has become clear that members of the FOX family have crucial roles in various aspects of immune regulation, from lymphocyte survival to thymic development. This review focuses on FOXP3, FOXN1, FOXJ1 and members of the FOXO subfamily and their function in the immune system.