Surviving a given infection requires the generation of a controlled immune response. Failure to establish or restore homeostatic conditions during or following the onset of an infection can lead to tissue damage. Investigation of the immunoregulatory network that arises in response to the infectious process or that is induced by the pathogen itself should provide insight into therapeutic approaches for the control of infection and any subsequent immunopathology. In this Review, I discuss current hypotheses and points of polemic associated with the origin, mode of action and antigen specificity of the various populations of regulatory T cells that arise during infection.