Crohn’s disease and ulcerative colitis are inflammatory bowel diseases (IBD) of unknown pathogenesis, for which no curative treatment is currently available. Although the recent introduction of agents designed to neutralise tumour necrosis factor has been an important achievement towards the control of Crohn’s disease, further development of more fundamental and non-toxic therapies is still required. One potential approach is the targeting of costimulatory membrane interactions between cells of the immune system. Costimulatory transmembrane ligands interact with receptors on target cells to enhance activation of the latter. Costimulatory interactions between antigen-presenting cells and T lymphocytes and between T lymphocytes and effector macrophages are of utmost importance for the activation of these cell types, which are all thought to be pivotal players in the immunopathology of IBD. Targeting these interactions with humanised monoclonal antibodies or soluble receptor fusion proteins is proposed as a potential new treatment modality of these often devastating pathologies. On the basis of experimental data, and in view of their essential role in the activation of antigen-presenting cells and T lymphocytes, the CD40/CD40 ligand and CD28/B7 interactions are likely to be the best targets for successful therapy.