This article highlights the discussion of the issues that had been raised during the International Life Sciences Institute North America- and USDA Agricultural Research Service-sponsored workshop surrounding the consumption of fructose. One conclusion of the discussion was that the metabolic effects of high-fructose corn syrup (HFCS) and sucrose appear to be similar in humans. However, there have been few studies directly comparing the effects of fructose to other caloric sweeteners, such as glucose, HFCS, and sucrose. Differential effects may include those related to insulin sensitivity, triglyceride and lipoprotein levels, and glycated protein levels. Further exploration of the differences between nutritive sweeteners should be the basis of a research agenda. Studies should also further investigate factors that might affect the results, such as the amount and form of the sweetener consumed, the macronutrient composition of the basal diet, the length of the study, and the characteristics of the subjects. Meanwhile, health professionals could help consumers by providing simple messages, such as the importance of consuming lower levels of energy, including those from all caloric sweeteners. J. Nutr. 139: 1269S-1270S, 2009.