Background: Sugars have emerged as one of the most important public health targets. Attention has focused on the special role of fructose based on its unique biochemical, metabolic, and endocrine responses. These mechanisms, however, have failed to translate into clinically meaningful effects in calorie-matched comparisons with other sources of carbohydrate. Sugars-sweetened beverage (SSBs) appear to be the special case. Whereas large prospective cohort studies have shown a consistent relation of SSBs with incident obesity, diabetes, metabolic syndrome (MetS), hypertension, coronary heart disease (CHD), stroke, and gout, associations have not been shown when modeling total sugars (with the exception of gout) or other food sources of added/free sugars such as pure fruit juices, yogurt, or even sweets. In the absence of a clear signal for sugars alone, it is unclear whether the associations seen for SSBs hold for other important food sources of sugars.