Chronic inflammation is a risk factor for several gastrointestinal malignancies, including colorectal cancer. Recent epidemiological studies and clinical trials demonstrate that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) markedly reduced the relative risk of colorectal cancer. Chronic inflammation associated with development of cancer is partly driven by the chemokine system. Chemokines are chemoattractant cytokines that recruit leukocytes from the circulatory system to local inflammatory sites. In this review, we highlight recent breakthroughs in our understanding of the role of chemokines in inflammatory bowel disease and colorectal cancer from animal models and human studies. These findings provide a rationale for the development of new anti-inflammatory therapeutic approaches for prevention and/or treatment of inflammatory bowel disease and colorectal cancer.