Thirty years ago, one of the first types of CD4+ T regulatory cells was discovered and named T regulatory type 1 (Tr1) cells. Tr1 cells represent a distinct population of T cells, which are induced in the periphery upon antigen exposure under tolerogenic conditions. They produce the immunosuppressive cytokines interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), do not constitutively express FOXP3, and suppress the function of effector immune cells. In this review, the key studies leading to the identification and biological characterization of Tr1 cells are recapitulated. The fundamental role of Tr1 cells in regulating immune responses to pathogenic and non-pathogenic antigens, as well as their use as cell therapeutics, is summarized. Advances in the field of T regulatory type 1 cell biology have revealed that they play a major role in dampening pathological immune responses. Roncarolo and colleagues review these advances and provide insight into the generation, function, and clinical utility of these cells for the treatment of immune-mediated diseases. © 2018 Elsevier Inc.