The prevalence of obesity over the past 20 years has reached staggering proportions, both in the United States and worldwide [1]. It is now estimated that 60% of American adults are overweight (BMI> 25) and 30% are obese (BMI> 30). Similarly, co-morbidities and mortalities related to obesity, such as Type 2 diabetes mellitus, hyperlipidemia, hypertension, and atherosclerotic vascular disease, are rising in parallel. This has occurred in spite of voluminous information and disseminated public education on the evils of excessive caloric intake in the form of high fat, low fiber, or high carbohydrate diets, and of sedentary lifestyles. Lately, the rate of increase in prevalence of childhood obesity has even outstripped that of adult obesity [2]. As Dr. Kaufman’s review in this volume attests, Type 2 diabetes mellitus, once thought almost non-existent below the age of 18, now accounts for fully one-third of all childhood diabetes mellitus, and is clearly correlated with the rise in obesity in childhood. Prevention and treatment of obesity has now taken center stage as our biggest public health problem, overtaking AIDS and accident prevention.

In evaluating obesity, Newton’s First Law of Thermodynamics, as interpreted by Maxwell, prevails: energy is neither created nor destroyed, but can be transformed into matter, and vice-versa. In human terms, caloric intake= energy expenditure+ weight gain. This had led to the concept that in order to promote weight loss, diet and exercise are all that are necessary to treat the majority of obese persons. But obesity is not that simple; it does not have one etiology, one pathogenesis, and certainly not one treatment. Although diet and exercise remain the mainstays of therapy for most patients, there clearly exists a subpopulation of obese subjects who appear not to be able to lose weight, irrespective of behavioral or lifestyle alterations.