Colorectal cancer continues to be a major cause of tumor mortality in the United States and other countries; despite attempts to improve the screening of high-risk populations, the incidence of this disease is still very high. Therefore, chemoprevention continues to be an important goal for the primary prevention of colorectal cancer. Among recent chemopreventive approaches, the administration of calcium and vitamin D continue to be evaluated in both preclinical and clinical studies. Many experimental findings described below have indicated associations between high calcium and vitamin D intake and decreased risk for colorectal cancer.