Metabolic syndrome, as manifested by visceral obesity, hypertension, insulin resistance, and dyslipidemia, is reaching epidemic proportions in the Western World, specifically the United States. Epidemiologic studies suggest that the increased prevalence of metabolic syndrome directly correlates with an increase in the consumption of fructose, mainly in the form of high-fructose corn syrup. This inexpensive alternative to traditional sugar has been increasingly utilized by the food industry as a sweetener since the 1960s. While augmented caloric intake and sedentary lifestyles play important roles in the increasing prevalence of obesity, the pathogenesis of hypertension in metabolic syndrome remains controversial. One intriguing observation points to the role of salt in fructose-induced hypertension. Recent studies in rodents demonstrate that increased dietary fructose intake stimulates salt absorption in the small intestine and kidney tubules, resulting in a state of salt overload, thus setting in motion a cascade of events that will lead to hypertension. These studies point to a novel interaction between the fructose-absorbing transporter, Glut5, and the salt transporters, NHE3 and PAT1, in the intestine and kidney proximal tubule. This paper will focus on synergistic roles of fructose and salt in the pathogenesis of hypertension resulting from salt overload.