The increasing recognition of obesity as a disease is compelling physicians and other health care workers to focus on the clinical management of obese patients using the available behavioral and pharmacologic management tools. Promising new approaches apply novel telecommunications strategies, mathematical energy balance modeling methods, exercise protocols, and dietary treatments to achieve weight loss and subsequent weight maintenance. The molecular mechanisms that underlie the weight loss observed with these therapies are being elucidated and giving rise to new insights on individual body composition and metabolic responses. Molecular target identification is promoting the search and identification of new pharmacologic treatments and strategies for reducing appetite and increasing energy expenditure. This collective research thrust in developing non-surgical management tools for treating obesity will be reviewed.