Colorectal cancer (CRC) is the one of the leading causes of cancer-related deaths in the world. CRC is responsible for more than 600,000 deaths annually and incidence rates are increasing in most of the developing countries. Epidemiological and laboratory investigations suggest that environmental factors such as western style dietary habits, tobacco-smoking, and lack of physical activities are considered as risks for CRC. Molecular pathobiology of CRC implicates pro-inflammatory conditions to promote the tumor malignant progression, invasion, and metastasis. It is well known that patients with inflammatory bowel disease are at higher risk of CRC. Many evidences exist reiterating the link between Inflammation and CRC. Inflammation involves interaction between various immune cells, inflammatory cells, chemokines, cytokines, and pro-inflammatory mediators, such as cyclooxygenase (COX) and lipoxygenase (LOX) pathways, which may lead to signaling towards, tumor cell proliferation, growth, and invasion. Thus, this review will focus on mechanisms by which pro-inflammatory mediators and reactive oxygen/nitrogen species play a role in promoting CRC. Based on these mechanisms, various preventive strategies, involving anti-inflammatory agents, such as COX inhibitors, COX-LOX inhibitors, iNOS inhibitors, natural supplements/agents, and synthetic agents, that blocks the inflammatory pathways and suppress CRC are discussed in this review.