In the face of an apparently increasing incidence of postmenopausal breast cancer, and with frustratingly limited gains in treatment, significant possibilities for widespread prevention of breast cancer must be vigorously explored. However, progress with this approach has been painfully slow, and the multifactorial etiology of breast cancer development is most responsible for this delay. The challenges in our approaches are to recognize the major differences between treatment and prevention and to demand a comprehensive biological rationale, an absence of serious toxic effects and likely long-term acceptability to women of interventions coming to definitive clinical trial.