Randomized controlled trials are recognized as having the strongest type of study design for generating evidence on prevention of disease. They are, however, the most labor- and time-intensive and costly to conduct. Intervention studies on the recurrence of colorectal adenomas might serve as a model with relevance to the etiology of not only large bowel cancer but also other sites of neoplastic development. The results of intervention studies assessing the effect of calcium, antioxidants and fiber on the recurrence of colorectal adenomas have been conflicting, showing a beneficial effect in some cases but not others. There are methodological issues in intervention trials for colorectal cancer, regarding study subjects, end point, dose, interaction, duration and timing, and compliance, for example. Although relatively few trials have been conducted to investigate the effects of an explicit dietary change on the recurrence of adenoma, results obtained so far have demonstrated that modifying the lifestyle may reduce the risk of chronic diseases including cancer. Furthermore, recent progress in molecular epidemiology has allowed clarification of many of the molecular mechanisms underlying susceptibility. Eventually, it may be possible to target intervention programs to genetically susceptible individuals, including molecular targeting, for the prevention of cancer.