Obesity is a rapidly increasing, worldwide epidemic. Despite recent scientific advances, no currently recommended dietary program or medication results in long-term weight loss of more than 10% of body weight for the vast majority of people who attempt these interventions. Hence, surgical intervention is recommended for patients with a BMI > or =40 kg/m2. Although surgery is an effective, sustainable treatment of obesity, it can be associated with potentially significant perioperative risks and long-term complications. Current research is focused on developing a medical therapy, which produces more effective and sustainable weight loss, yet avoids the risks inherent in major surgery. With a reduced risk profile, such therapy could also be appropriately offered to those who are less obese and, in theory, help those who have BMIs as low as 27 kg/m2. Toward that end, numerous scientists are working to both unravel the pathophysiology of obesity and to determine why surgical intervention is so effective. This review briefly examines the current status of obesity pathophysiology and management, the reasons for failure of conventional medical treatments, and the success of surgical intervention. Finally, future areas of research are discussed.