Colorectal cancer is the third most common cancer and the second leading cause of cancer death in the United States. Although environmental factors, including diet and lifestyle, clearly play a role in the etiology of colorectal cancer, as many as 25% of patients with colorectal cancer have a family history of the disease, which suggests the involvement of a genetic factor. Inherited colon cancers can be divided into two main types: the well-studied but rare familial adenomatous polyposis (FAP) syndrome, and the increasingly well-characterized, more common hereditary nonpolyposis colorectal cancer (HNPCC, a.k.a. Lynch Syndrome). The prevention, screening, diagnosis, and treatment of cancers of the colon and rectum are covered in this chapter. Figures illustrate various forms of adenomatous polyps, the tumor, node, metastasis (TNM) staging system for colorectal cancer, and the five-year survival rate in patients with colorectal carcinoma. Tables describe risk factors; possible chemopreventive agents; evidence supporting the effectiveness of screening tests; features and usage issues with different fecal occult blood tests; recommendations for early detection, screening, and surveillance for patients at different levels of risk; colorectal cancer staging systems; indicators of poor prognosis; and chemotherapeutic and biologic agents in the treatment of colorectal cancer. This chapter contains 197 references.