Immunogenicity, or the formation of anti-drug antibodies (ADAbs), has been described in response to all biologic therapies licensed for rheumatoid arthritis (RA). In patients treated with monoclonal antibodies, immunogenicity may be associated with low serum drug levels, loss of therapeutic response, poor drug survival and/or adverse events such as infusion reactions. In this chapter we review the factors that may predispose to immunogenicity to biologics as well as mitigating factors in RA such as the effect of concomitant non-biologic DMARDs. The reported incidence of ADAbs varies greatly depending on techniques used for measurement. The interpretation of these is discussed followed by the effect of anti-drug antibodies and drug levels on drug efficacy and safety of biologics in RA. Finally we evaluate the evidence to date on the impact of biosimilar switching on immunogenicity and tolerising to ADAbs.