Weight loss can be achieved by any means of energy restriction, but the challenge is to achieve sustainable weight loss and prevent weight "creep" without increasing the risk of chronic disease. The modest success of low fat diets has prompted research on alternative dietary strategies, including high protein diets and low glycemic index (GI) diets. Conventional high carbohydrate diets, even when based on wholegrain foods, increase postprandial glycemia and insulinemia and may compromise weight control via mechanisms related to appetite stimulation, fuel partitioning, and metabolic rate. This paper makes the case for the benefits of low glycemic index diets over higher protein diets. Both strategies are associated with lower postprandial glycemia, and both are commonly labeled as "low glycemic load," but the long-term health effects are likely to be different. A large body of evidence, which now comprises observational prospective cohort studies, randomized controlled trials, and mechanistic experiments in animal models, provides robust support for low GI carbohydrate diets in the prevention of obesity, diabetes, and cardiovascular disease. Although lower carbohydrate, higher protein diets increase the rate of weight loss, cohort studies and meta-analyses of clinical trials suggest the potential for increased mortality.