The notion of developing cancer preventative strategies is attractive both from a public health and from a health economic viewpoint. However, as currently visualized, this may involve dietary supplementation of publicly available foods or the ingestion of specific supplements for prolonged periods of time. In view of the fact that the outcome of such preventative strategies may as yet not be known, it is essential that the strategy is devoid of risks. Structure-activity relationship (SAR) concepts can be of use in identifying possible health hazards associated with chemoprevention. Overall, SAR can be used (1) to predict the chemopreventative potential of a chemical and to understand its mechanism of action, (2) to evaluate the toxicological liabilities of such agents and (3) to design molecules with enhanced chemopreventative potency and decreased (or abolished) toxicity. While SAR techniques currently available are appropriate to achieve these aims, the primary block to their widespread deployment is lack of sufficient experimental data of acceptable quality to perform SAR modeling. The present report analyzes the current applicability of SAR methods to cancer chemoprevention.