Insulin-like growth factor I (IGF-I) and its main binding protein 3 (IGFBP-3) are multi-regulatory peptides important in tumour cell growth and survival. In the circulation, they occur in large quantities and are readily measured. Across a population, concentrations vary and this may impact on risk of cancers common in western societies. Emerging epidemiological evidence supports the notion that higher levels of IGF-I are associated with increased risk of pre-menopausal, but not post-menopausal, breast cancer. Higher levels of IGFBP-3 may also predict for increased risk of pre-menopausal breast cancer, but this is contrary to the conventional view that this peptide is tumour protective. Nutritional and lifestyle factors, important in breast cancer risk, also inter-relate with circulating levels of IGF-I, but in many circumstances, the relationships are complex. It is becoming increasingly important that the clinical breast oncologist understands the physiology of the IGF system and its potential role in cancer risk assessment and prevention.