A Western lifestyle--characterized by low physical activity, and high dietary intake, animal protein, saturated fats and rapidly digestible carbohydrates--is associated with increased risks of many cancers. It has been postulated that, at least in part, these increases may be mediated by alterations in the metabolism of insulin and insulin-like growth factors (IGFs), related to nutritional lifestyle. Insulin regulates energy metabolism and increases the bio-activity of IGF-1 by enhancing its synthesis and by decreasing several of its binding proteins (IGFBP-1 and 2). Insulin and IGF-1 both stimulate anabolic processes as a function of available energy and elementary substrates (e.g. amino acids). The anabolic signals by insulin or IGF-1 can promote tumour development by inhibiting apoptosis, and by stimulating cell proliferation. Epidemiological evidence is accumulating and suggests that the risk of cancers of the colon, pancreas, endometrium, breast and prostate are related to circulating levels of insulin, IGF-1, or both. Nutritional energy balance, macronutrient composition of the diet and physical activity levels appear to be major determinants of IGF-1 bioactivity.