Immune tolerance therapies are designed to reprogramme immune cells in a highly specific fashion in order to eliminate pathogenic responses but preserve normal immune function. A concept that has tantalized immunologists for decades, tolerogenic therapies would replace current lifelong immunosuppressive regimens and their often debilitating side–effects with short–term immunosuppressive regimens and their often debilitating side–effects with short–term, effective cures. Significant advances have been made over the past decade that have provided a more detailed understanding of the molecular events associated with T–cell recognition and activation. Unprecedented opportunities to test these approaches in a variety of human diseases have now emerged. As a result of these advances, the Immune Tolerance Network (ITN), a group of 70 expert immunologists spanning multiple disciplines, has been created to identify and promote the use of tolerogenic therapies in the clinic. Using a unique interactive approach designed to speed the development of clinical tolerance therapies, the ITN is examining new and innovative therapeutic approaches and bioassays in a range of autoimmune diseases and transplantation settings, as well as asthma and allergies. This work has been funded by the National Institutes of Health (in collaboration with the Juvenile Diabetes Foundation International).