Chronic inflammatory disorders are often associated with an increased risk of developing cancer. A classic example of the connection between inflammation and cancer is the increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). In this review, we discuss aspects of IBD that promote colorectal cancer and highlight key molecular mediators that contribute to cancer risk. Additionally, we report on progress in identifying molecular targets that may prove efficacious in blocking the progression of IBD-related inflammation to cancer.