Excess adiposity and obesity are the root cause of at least 27 diseases that cause considerable lifelong morbidity and, in many scenarios, eventual cardiovascular mortality. The human body has the ability to increase the number and size of its adipocytes by approximately 10-fold over the course of a lifetime. As fat mass increases, its blood supply, supporting cells, tissue structure, and local and systemic hormonal control also increase. This results in excess adiposity, leading to progressive obesity and the resistance to weight-loss attempts. There have been numerous trials of food diets combined with exercise that, in general, have a 50% dropout rate at 1 year and lead to very modest (~ 5%) reductions in body weight. Thus, many with obesity require interventions beyond casual diet and exercise advice. Meal replacement diets and bariatric surgery offer considerably greater degrees of weight loss, but both can be plagued by weight regain. Because the ability to control food urges has been shown to be a key psychological factor for success, medicinal approaches that work in this domain are attractive adjuncts to diet, exercise, and weight-loss surgery. This article reviews the emerging role of medical therapy in the treatment of excess adiposity with the goal of reducing comorbidities and possibly improving cardiovascular survival.