A promising therapeutic approach for inducing tolerance in autoreactive T cells is the use of APCs such as DCs and macrophages. In this issue of the European Journal of Immunology, Zheng et al. [Eur. J. Immunol. 2013. 43: 219–227] study the concept of “tolerogenic adjuvants” to induce tolerance via vaccination. These authors have previously identified dexamethasone (Dex) as an effective “tolerogenic adjuvant” and, in this study, they have identified a population of peripheral macrophages that is enriched by Dex treatment and that mediates Dex's tolerogenic effect. In addition to performing a phenotypic characterization of this population, the authors noted an increase in serum levels of IL-10 and Treg cells after Dex treatment of mice. As discussed in this Commentary, by employing Dex as a tolerogenic adjuvant in the presence of relevant peptides, we may have a means of restoring specific immune tolerance in cases of autoimmune disease and allergy.