Cancer prevention trials are contrasted with cancer therapy trials, cardiovascular disease prevention trials, epidemiologic cohort and case-control studies, and trials with surrogate endpoints, in order to highlight some of their unique features and in order to examine the role of such trials in the cancer prevention agenda. The implication of these features and this role are discussed with respect to trial rationale, trial design, and trial protocol, with planning exercises for proposed dietary fat intervention trials among women providing illustration. Finally, some considerations are mentioned for the planning of a primary prevention trial of breast cancer using tamoxifen.