Current options to treat inflammatory bowel diseases (IBDs) are often associated with undesired side effects, have limited therapeutic benefit for many patients and do not lead to a complete restoration of the mucosal immune balance. Recent research progress in the pathogenesis of IBDs has widely broadened our understanding of the complex nature of these immunological disorders and identified new potential therapeutic targets. New insights into the molecular mechanisms underlying IBDs may now allow the development of new in vivo or ex vivo therapeutic gene treatment strategies that alter the biological functions of cells in the inflamed gastrointestinal tract. New gene transfer approaches based either on blocking pro-inflammatory cytokines or overexpression of anti-inflammatory cytokines, particularly interleukin-10, showed promising results in animal models of IBD. Future studies analyzing the effects of cytokine-targeted gene therapy in patients are eagerly awaited.