Over the past five years there has been an explosion of “targeted therapies” for cancer treatment. In most cases, these therapies have been based on pre-clinical data showing that specific molecules play an important role in regulating the malignant phenotype. In breast cancer, there is compelling rationale that such targeted strategies should be successful. Targeting of estrogen receptor ? (ER?) has proven to be a successful way to reduce breast cancer risk, decrease the risk of death and recurrence in an adjuvant setting, and remains the first choice of treatment for advanced disease. With this success, it is hoped that other molecular pathways could also be successfully exploited. This publication reviews the role of the insulin-like growth factors (IGFs) in breast cancer. Over 100 years ago George Beatson made an intuitive leap connecting breast cancer therapy with ovarian function He removed the ovaries from a premenopausal woman with breast cancer; he reasoned that ovarian function regulated normal mammary gland function, therefore the ovaries may influence the malignant phenotype. Other discussion included cover the function of IGF action in the normal mammary gland using mouse model systems where expression and function can be manipulated and the patterns of expression of the IGFs, their binding proteins, and their receptors in the normal gland.