Insulin-like growth factors (IGFs) are mitogenic and anti-apoptotic peptides that influence the proliferative behavior of many cell types, including normal and transformed breast epithelial cells. IGF-I has properties of both a tissue growth factor and a systemic hormone: there is evidence that IGF bioactivity in tissues is influenced not only by local factors such as tissue expression of IGFs, IGF binding proteins (IGFBPs), and IGFBP proteases, but also by factors that regulate whole-body IGF physiology and circulating IGF-I levels. Experimental evidence that interventions that reduce circulating IGF-I levels reduce proliferation of breast neoplasms has raised interest in the possibility of developing novel endocrine therapies that target the growth hormone/IGF-I axis. Furthermore, influences of the growth hormone/IGF-I axis on normal breast epithelial cells may underlie recent epidemiological observations that suggest that premenopausal women with high circulating IGF-I level are at increased risk for breast cancer. These studies suggest that the growth hormone/IGF-I axis deserves investigation as a possible target for novel breast cancer prevention strategies.