Disease modifying strategies and biologics are available for treatment of rheumatoid arthritis (RA), and optimal response rates are achieved at onset. Several trials have explored the possibility of preventing RA by administering current drugs to at-risk patients. These trials demonstrate that a short course of treatment during the pre-clinical period can delay onset of RA – but does not produce drug-free remission or cure. Thus, the current approach of moving treatment with conventional drugs earlier in the disease course extends the time of treatment, rather than prevents disease. With novel immunotherapies showing promise to restore long-term immune tolerance safely in early-stage clinical trials for patients with autoimmune diseases, we have now an unprecedented window of opportunity to test their potential to prevent the onset of RA and other autoimmune diseases in high-risk individuals, identifiable by risk-scores and other disease-associated biomarkers. Antigen-specific strategies promise greater specificity and safety, without general immune suppression, and thus the potential for intervention in at-risk subjects before disease onset. I will discuss our work and the clinical trial landscape, to examine the potential for antigen-specific tolerance strategies and behaviour intervention strategies to achieve personalised prevention of RA.