Crohn's disease is a chronic inflammatory bowel disease of unknown origin. The understanding of the pathogenesis of inflammatory bowel diseases has been greatly advanced by manipulations of the immune system in mice using targeted disruptions of genes that encode specific anti- and proinflammatory cytokines, as well as T-cell subsets. The outcome of these experiments has implicated CD4+ lymphocytes and certain proinflammatory cytokines (tumour necrosis factor-alpha, interleukin-12) as playing a central role in the pathogenesis of mucosal inflammation in Crohn's disease. The present review focuses on these recent important immunological observations, and discusses several newly developed therapeutic strategies that are based either on blocking proinflammatory cytokines or on the administration of anti-inflammatory cytokines.