Tolerising immunotherapy including antigen-specific immunotherapy (ASI) holds great promise for autoimmune diseases, where there are limited treatment options and/or scope for prevention. These diseases include rheumatoid arthritis (RA) and type 1 diabetes (T1D). Preclinical success for this approach has been demonstrated in vivo, and promising evidence for various strategies that restore immune regulation is beginning to emerge from clinical trials in people at risk and after onset of autoimmune diseases. Hurdles include the development of robust prognostic and predictive biomarkers for therapeutic outcome and identification of the most appropriate population and timing of intervention. ASI promise greater specificity and safety than non-ASI, and thus great potential for autoimmune disease interception in high-risk individuals. I will discuss my personal journey developing and trialling innovative therapeutics for tolerising ASI in autoimmune diseases, including the development and use of biomarkers. I will demonstrate how the results of our clinical studies and trials in RA and T1D open new insights into the concept of tolerance, immunotherapeutic mechanisms of action, innovative use of biomarkers in clinical trials and therapeutic implementation of ASI.