Colorectal cancer is among the most common cancers worldwide, in terms of overall mortality. Environmental factors have been identified to play the most important roles in the development of this disease, in particular diet and its specific components. Selenium is an important micronutrient engaged in the protection of colonic cells against a wide range of external and internal stressors. In addition, selenium has been reported to actively inhibit growth of malignant colonic cells as well as to induce their demise. Furthermore, besides its promising chemopreventive role in the various stages of colorectal cancer development, selected chemical forms of selenium have shown interesting interaction patterns with some cytostatic chemicals or inducers of apoptosis. The advantages of selected selenium preparations thus might reach beyond chemoprevention since they may be used in conjunction with established antioneoplastic drugs, thereby establishing new treatment modality for colorectal cancer. In addition to summarizing our current knowledge about the mechanisms whereby selenium imparts its chemopreventive potential in colon carcinogenesis, the possibilities of a combined use of selenium with other cytostatics and chemicals are discussed.