Refined sugars have only relatively recently appeared in the diets of most people. Regulatory pathways that balance calorie intake and energy expenditure and reward pathways help the body regulate ingestion of these sweeteners, as well as other foods. The overconsumption of refined sugars, including sucrose and fructose, in beverages and prepared foods, undoubtedly contributes to the obesity epidemic that is escalating in the United States and throughout other industrialized countries around the world. Obesity is also linked to inactivity, economic considerations, and the ready availability of food, but is the real problem that these sweeteners act like a drug, leading to a cycle of food use and reward and addiction?