Dietary energy restriction (DER) inhibits the development of spontaneous, chemically, genetically, and virally induced mammary cancer in rats and/or mice. DER inhibits the initiation and postinitiation stages of mammary carcinogenesis and the development of both ovarian-hormone-dependent and -independent mammary carcinomas. The predominant effect of DER appears to be suppression of the clonal expansion of transformed cells, and this effect is most likely mediated via the coordinated regulation of cell proliferation, apoptosis, and angiogenesis. The effects of DER on cell cycle regulation and apoptosis are consistent with the limitation of one or more cell survival factors. Evidence is presented that the chemical mediators of this effect, glucocorticoids, insulin, and/or insulin-like growth factors, are elicited in response to the limitation in glucose availability imposed by DER. Investigation of DER is highly relevant to the misregulation of body weight which has been identified as a human health problem of global proportion. Mechanistic studies hold the promise of leading to the identification of DER mimetic approaches that can be used in the prevention and control of breast cancer.