Emerging data suggest that the monosaccharides, glucose and fructose, have disparate effects on the neuroendocrine circuits involved in appetite and reward processing. Compared to glucose, fructose ingestion results in smaller increases in circulating levels of insulin, leptin, and glucagon-like polypeptide-1, hormones that increase satiety. The central administration of fructose was shown to decrease hypothalamic satiety signaling and increase feeding in animals, whereas glucose increased satiety signaling and reduced food intake. Likewise, studies show that the hypothalamus responds differently to fructose versus glucose ingestion in humans. Moreover, fructose compared to glucose results in greater food-cue reactivity within brain reward regions and increases the motivation for food rewards. These findings provide insights into how neuroendocrine responses to specific carbohydrates may influence eating behavior.