Despite improvement in outcomes, loss of response (LOR) to tumor necrosis factor-alpha (TNFα) therapies is a big concern in the management of inflammatory bowel disease. LOR is associated with flares of disease, increased hospitalisation rates, need for surgical interventions, and decline in quality of life. LOR may be multifactorial, but immunogenicity makes a significant contribution. Traditionally doses of anti-TNFα have been adjusted based on clinical response, using a standard approach. Immunomonitoring involves the measurement of anti-TNFα trough and antibody levels. It takes into account the underlying pharmacokinetics of anti-TNFα therapies. Expanding on this a treat to target approach may be used, where doses are intensified, or tailored to the individual based on the measurement of anti-TNFα trough and antibody levels. This review looks at the history, evolution, and clinical impact that immunomonitoring is having in the treatment of inflammatory bowel disease. It will focus on the role of immunomonitoring in helping to achieve long lasting deep remission and mucosal healing. It will explore the different options in terms of best measuring trough and antibody levels, explore possible advantages of immunomonitoring, and discuss its role in best optimising response, at induction, during the maintenance phase of treatment, as well as a role in withdrawing or switching therapy.