Excess weight gain occurs when more calories are consumed than expended over a long period of time. Accurate translation between changes in calories and changes in weight is important for setting goals and for evaluating interventions at both the individual and population levels. For years, a simple rule of thumb has been used for predicting weight change: 3,500 calories equals one pound of body weight change. However, emerging research demonstrates that the math is not that straightforward, and the 3,500-calorie rule will create overly optimistic predictions of weight loss, oftentimes being in error by many fold. This brief presents new mathematical models that can be used to calculate the impact of calories on body weight in both adults and children, and several useful rules of thumb that can estimate changes at the population level. These models suggest that the obesity epidemic was driven by much larger changes in calorie intake than previously believed and will require aggressive strategies to reverse.