There has been much concern regarding the role of dietary fructose in the development of metabolic diseases. This concern arises from the continuous increase in fructose (and total added caloric sweeteners consumption) in recent decades, and from the increased use of high-fructose corn syrup (HFCS) as a sweetener. A large body of evidence shows that a high-fructose diet leads to the development of obesity, diabetes, and dyslipidemia in rodents. In humans, fructose has long been known to increase plasma triglyceride concentrations. In addition, when ingested in large amounts as part of a hypercaloric diet, it can cause hepatic insulin resistance, increased total and visceral fat mass, and accumulation of ectopic fat in the liver and skeletal muscle. These early effects may be instrumental in causing, in the long run, the development of the metabolic syndrome. There is however only limited evidence that fructose per se, when consumed in moderate amounts, has deleterious effects. Several effects of a high-fructose diet in humans can be observed with high-fat or high-glucose diets as well, suggesting that an excess caloric intake may be the main factor involved in the development of the metabolic syndrome. The major source of fructose in our diet is with sweetened beverages (and with other products in which caloric sweeteners have been added). The progressive replacement of sucrose by HFCS is however unlikely to be directly involved in the epidemy of metabolic disease, because HFCS appears to have basically the same metabolic effects as sucrose. Consumption of sweetened beverages is however clearly associated with excess calorie intake, and an increased risk of diabetes and cardiovascular diseases through an increase in body weight. This has led to the recommendation to limit the daily intake of sugar calories.Pure, white, and deadly: the dark side of sugar was suspected many years ago, when an association between sugar consumption and coronary heart diseases was recognized and emphasized by John Yudkin [1]. Sugar, a natural sweetener obtained from either sugar cane or beets, is a disaccharide composed of one glucose molecule linked through an α1-4 glycoside bond to a fructose molecule. Fructose, besides contributing to half the total content of sugar, can also be found as a hexose in fruits and honey. More recently, sweeteners started to be produced from corn through starch isolation and hydrolysis to glucose, followed by enzymatic isomerization of part of the glucose into fructose [2,3]. The resulting mixture, known as high-fructose corn syrup (HFCS), has several industrial advantages over sugar, the most important being its low price, and has progressively replaced sugar consumption in North America over the past 30 years.Fructose metabolism has been reviewed extensively elsewhere [4][5][6] and will be only briefly outlined here. In the gut, fructose is transported by specific transporters, GLUT5 [7,8]. In some subjects, fructose absorption is quantitatively limited, and some malabsorption occurs when lar...