The insulin-like growth factor (IGF) system is related to proliferation and tumor growth, and high levels of circulating IGF-I are thought to be a risk factor for several types of cancer. This review summarizes the epidemiologic evidence for an association between circulating IGF-I and cancer risk as well as the experimental evidence for a causal relation between the endocrine IGF system and tumor growth. The potential for dietary intervention to alter the IGF system and thereby cancer risk is supported by several lines of evidence. Postulated mechanisms of action are as follows: (a) reduction of levels of circulating IGF-I, which will decrease activation of the IGF-I receptor and subsequent signaling pathways; (b) increasing local IGF binding proteins, which may have IGF-dependent effects through obstruction of IGF interaction with local IGF-I receptor as well as IGF-independent effects; and (c) interference with estrogens and estrogen receptor action, which may have direct (and possibly synergistic) effects on IGF signaling. An overview is given of the epidemiologic studies on dietary determinants of circulating IGF-I. Examples of dietary factors, such as dairy protein, lycopene, and phytoestrogens, are used to illustrate the potential mode of action of dietary interventions that may act on the IGF system. In conclusion, the IGF system has every potential to serve as an intermediate for cancer (chemo)prevention studies. On the short term, more research initiatives aimed at the effects of specific food components or dietary strategies on the IGF system both in animal models and in humans are warranted.