Over the past 20 years, obesity has represented a significant focus of research conducted in Clinical Research Centers (CRCs) in the United States. This review will focus on the progress in our understanding of the disease that CRC-based research has produced; therefore, the reference list is not exhaustive and consists primarily of CRC-based research. Obesity is defined as an excess of body fat as measured by triceps skinfold thickness. The time of onset of obesity is an important factor, for example, early onset is associated with an increase in the number of fat cells. Weight loss reduces the size but not the number of fat cells. Type II diabetes mellitus is a common complication in obese adults; this condition has been related to fat cell size and, in women, to predominantly upper-body fat distribution. Pregnant obese women and their babies are at risk for a number of problems. Abnormalities commonly found in obese persons include increased plasma lipid levels, hyperinsulinism, increased cholesterol synthesis, high frequency of gallstones, and hypertension. Under a variety of experimental conditions, the only difference in the response of obese and normal weight subjects to food was that the obese subjects appeared to consume more, but other data suggest that the obese may have greater energy needs. Carbohydrate intake has been studied extensively. Metabolic rate increases with overfeeding, especially in response to carbohydrate. Basal metabolic rates are higher in obese adults and rise in response to overfeeding; they decrease after weight reduction. This decrease can be counteracted with sucrose, perhaps because sucrose maintains triiodothyronine levels. Obese persons may be less able to dispose of excess calories. Carbohydrate-free diets have received intensive investigation, and the importance of high quality protein intakes and adequate mineral supplementation have been documented. Nonetheless, because of the limited success of hypocaloric diets for the severely obese, various surgical approaches have been explored.