CD4+ T-lymphocytes have a central role in the pathogenesis of Crohn's disease. The activation and proliferation of T-lymphocytes following stimulation by antigen-presenting cells is controlled by regulatory cytokines (i.e. IL-10) and by induction of programmed cell death. Tissue damage as a result of T-lymphocyte-mediated inflammation is mediated by pro-inflammatory cytokines, including TNF-α. Novel immunodulatory strategies in Crohn's disease are based on these principles, and it has been demonstrated that neutralization of TNF-α by administration monoclonal antibodies as well as administration of recombinant human IL-10 have therapeutic activity in Crohn's disease. The current status of these new therapies as well as future developments are discussed.