In addition to acquiring a better understanding of foods that may have intrinsic health benefits, increasing our knowledge of dietary components that may adversely impact health and wellness, and the levels of consumption at which these adverse effects may occur, should also be an important priority for the Foods for Health initiative. This review discusses the evidence that additional research is needed to determine the adverse effects of consuming added sugars containing fructose. Current guidelines recommend limiting sugar consumption in order to prevent weight gain and promote nutritional adequacy. However, recent data suggest that fructose consumption in human results in increased visceral adiposity, lipid dysregulation, and decreased insulin sensitivity, all of which have been associated with increased risk for cardiovascular disease and type 2 diabetes. A proposed model for the differential effects of fructose and glucose is presented. The only published study to directly compare the effects of fructose with those of commonly consumed dietary sweeteners, high fructose corn syrup and sucrose, indicates that high fructose corn syrup and sucrose increase postprandial triglycerides comparably to pure fructose. Dose-response studies investigating the metabolic effects of prolonged consumption of fructose by itself, and in combination with glucose, on lipid metabolism and insulin sensitivity in both normal weight and overweight/obese subjects are needed.