Nuclear factor (NF) kappa B is a transcription factor that controls the transcription of a variety of cellular genes regulating the inflammatory response. Many proinflammatory cytokines are transcriptionally regulated by NF-kappa B, and their increased expression has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Even though it seemed clear that the increase in proinflammatory cytokine production in IBD is crucial for the initiation and perpetuation of chronic intestinal inflammation, the elements governing this dysregulation of enhanced cytokine production remained unclear. This review discusses a series of recent studies that demonstrate the activation of NF-kappa B in the inflamed mucosa, and that shed new light on the central pathogenic role of NF-kappa B in chronic intestinal inflammation. In addition to describing the activation of NF-kappa B, excitement has been generated by reports that define the molecular targets of anti-inflammatory agents, and that demonstrate the effective blockade of NF-kappa B in intestinal inflammation. These new insights into the activation and inhibition of NF-kappa B have opened new and promising avenues for a more specific treatment of chronic intestinal inflammation.