Prospective studies suggest that individuals with circulating levels of insulin-like growth factor 1 (IGF-1) at the high end of the normal range are at increased risk for several common cancers. Further data implicate IGF-1 and hyperinsulinism as candidate mediators of the effects of body size on cancer risk and prognosis. Ongoing research seeks to confirm these findings, to clarify the underlying physiology, and to assess their relevance to patterns of cancer incidence. In vivo models have not only provided data consistent with the epidemiological observations, but also suggest that IGF-1 signalling stimulates growth of established cancers. This has led to the development of novel IGF-I receptor targeting therapies which have impressive antineoplastic activity in experimental systems.