Although the precise etiology of inflammatory bowel diseases (IBD) still remains unclear, considerable progress has been made in the identification of novel signal transduction pathways that elucidate the immunopathogenesis involved in the perpetuation of the inflammatory process. As both ulcerative colitis and Crohn's disease are associated with an increased risk for developing colorectal cancer (CRC) and precancerous dysplastic epithelial changes, further studies have concentrated on finding a common signaling pathway that could serve as a mechanistic link between inflammation and associated colonic cancer in IBD. This review presents the current data concerning the pathogenic role of the IL-6/STAT-3 trans signaling pathway in IBD and colorectal cancer. Furthermore it evaluates the possible therapeutic potential of targeting this pathway for the therapy of IBD and CRC.