IBD treatment is undergoing a transformation with an expanding repertoire of drugs targeting 
different aspects of the immune response. Three novel classes of drugs have emerged in the past 
decade that target leukocyte trafficking to the gut (vedolizumab), neutralize key cytokines with 
antibodies (ustekinumab) and inhibit cytokine signalling pathways (tofacitinib). In advanced 
development are other drugs for IBD, including therapies targeting other cytokines such as IL-23 and 
IL-6. However, all agents tested so far are hampered by primary and secondary loss of response, so 
it is desirable to develop personalized strategies to identify which patients should be treated with 
which drugs. Stratification of patients with IBD by clinical parameters alone lacks sensitivity, and 
alternative modalities are now needed to deliver precision medicine in IBD. High-resolution 
profiling of immune response networks in individual patients is a promising approach and different 
technical platforms, including in vivo real-time molecular endoscopy, tissue transcriptomics and 
germline genetics, are promising tools to help predict responses to specific therapies. However, 
important challenges remain regarding the clinical utility of these technologies, including their 
scalability and accessibility. This Review focuses on unravelling some of the complexity of mucosal 
immune responses in IBD pathogenesis and how current and emerging analytical platforms might be 
harnessed to effectively stratify and individualise IBD therapy.