Obesity, with its comorbidities, is a major public health problem. Population-based surveys estimate 2 of every 3 U.S. adults are overweight or obese. Despite billions of dollars spent annually on weight loss attempts, recidivism is high and long-term results are disappointing. In simplest terms, weight loss and maintenance depend on energy balance, and a combination of increased energy expenditure by exercise and decreased energy intake through caloric restriction is the mainstay of behavioral interventions. Many individuals successfully lose 5%-10% of body weight through behavioral approaches and thereby significantly improve health. Similar success occurs with some weight loss prescriptions, although evidence for successful weight loss with over-the-counter medications and supplements is weak. Commercial weight loss programs have helped many individuals achieve their goals, although few programs have been carefully evaluated and compared, limiting recommendations of one program over another. For the very obese, bariatric surgery is an option that leads to significant weight loss and improved health, although risks must be carefully weighed. Lifestyle changes, including regular physical activity, healthy food choices, and portion control, must be adopted, regardless of the weight loss approach, which requires ongoing support. Patients can best decide the appropriate approach working with a multidisciplinary team, including their health care provider and experts in nutrition, exercise, and behavioral intervention.