BACKGROUND: Insulin sensitivity is a key function in human metabolism because it has a crucial role in the development of disease that are increasingly common in modern society. Impaired insulin sensitivity is an important determinant of type 2 diabetes; moreover, it has been proposed as an independent risk factor for cardiovascular disease. Thus, reduced insulin sensitivity is strongly associated with the metabolic syndrome, which represents a cluster of metabolic abnormalities and cardiovascular risk factor. Insulin sensitivity can be modulated by different environmental factors, including dietary habits. Obesity, especially if associated with abdominal adiposity, impairs insulin-sensitivity while physical activity can improve it; however, the composition of the habitual diet is clearly an important regulator of this function. AIM: To evaluate methodologies and markers that can be used to substantiate existing and potential claims of beneficial effects of foods on relevant functions connected with body fat deposition, insulin sensitivity and blood glucose regulation. RESULTS: We have reviewed the scientific basis for existing and potential claims, based not only on modifications of the target functions (body fat deposition, insulin sensitivity and blood glucose regulation) but also on modifications of other relevant associated functions (energy intake, energy expenditure, fat storage and oxidation, lipotoxicity, body fat composition, inflammation, oxidative stress, vascular function, glucose production and utilization). In this context we have identified a number of markers and evaluated appropriate method to measure and validate them. CONCLUSIONS: Relevant functions contributing to overweight, the metabolic syndrome and diabetes have been identified. The evidence reviewed indicates that in this field the link between nutrition, biological responses and diseases is clearly established. Therefore, there is a strong potential to develop functional food science. The major gap in the evidence continues to be the lack of diet based intervention trials of sufficient duration to be relevant for affecting the natural history of these conditions.