Rates of overweight and obesity have been on a steady rise for decades, and the problems society faces from this and associated metabolic diseases are many. As a result, the need to understand the contributing factors is great. A very compelling case can be made that excess sugar consumption has played a significant role. In addition, fructose, as a component of the vast majority of caloric sweeteners, is seen to be particularly insidious. Evidence shows that fructose bypasses many of the body's satiating signals, thus potentially promoting overconsumption of energy, weight gain, and the development on insulin resistance. It has also been shown to increase uric acid levels, which in turn promotes many of the abnormalities seen in the metabolic syndrome including hypertriglyceridemia. However, the main source of fructose in the diet is high-fructose corn syrup (HFCS), an artificially manufactured disaccharide that is only 55% fructose. This review highlights the fact that limited data are available about the metabolic effects of HFCS compared with other caloric sweeteners. The data suggest that HFCS yields similar metabolic responses to other caloric sweeteners such as sucrose.