Insulin-like growth factors (IGFs) play a fundamental role in somatic growth and cellular differentiation, metabolism and survival. Indeed, the processes linking nutrition, metabolism and growth are thought to involve a complex interrelation among insulin, growth hormone (GH), IGFs and their binding proteins (IGFBPs). However, accumulating data from both experimental and molecular epidemiological studies indicate that these growth factors may also be important in the pathophysiological processes underlying chronic disease, including type 2 diabetes mellitus, coronary heart disease and cancer. Experimental and observational studies suggest that higher levels of circulating IGF-I may increase risk of several cancers. By contrast, recent prospective epidemiological studies suggest that relatively higher IGF-I levels may reduce the risk of type 2 diabetes and coronary heart disease. However, these relatively small-scale observational studies are susceptible to chance, reverse causality and residual or unmeasured confounding. A 'Mendelian randomization' approach based on large-scale gene association and prospective observational studies might help determine the possible causal role of IGF-I and its binding proteins in the aetiology of type 2 diabetes, coronary heart disease and cancer.