Colorectal cancer (CRC) is the leading cause of cancer-related mortality in western countries. Adjuvant treatment does not seem to be highly effective and recurrent or metastatic disease occurs in half of the new cases within one year of diagnosis and median survival does not exceed 18 months. CRC represents an optimal model for primary and secondary prevention, given the availability of effective screening procedures and of a well defined multi-step carcinogenic pathway. Colon cancer is supposed to arise as the result of a series of genetic mutations, which parallel histopathologic and molecular changes, from normal colonic epithelium to invasive carcinoma, with adenomatous polyps as an intermediate step. A growing body of evidence has shown a wide variety of effective compounds, in vitro in animal models and in human clinical trials. The more studied agents are the non-steroidal anti-inflammatory drugs. Among those, aspirin has been shown, in two recent randomised trials, to lower the incidence on polyps vs. placebo. Intervention studies on diet showed disappointing results, but diet micronutrients are promising agents in CRC prevention. Calcium, vitamin D and folic acid in different proportions in different populations have been shown to have a certain degree of action in preventing cancer development in epidemiological studies and in randomised trials. Also oestrogens or, rather, hormone replacement therapy for the menopause can protect against CRC. In conclusion, the rapid growth of information and knowledge in chemoprevention, especially for CRC, is very encouraging and gives us hope that soon this approach will be applicable in a larger scale population.