Using the Guidelines for the Management of Overweight and Obesity in Adults as a framework, this article reviews intensive lifestyle interventions for weight loss. The Guidelines recommend a minimum of 6 months of high-intensity, comprehensive lifestyle intervention, consisting of a reduced-calorie diet, increased physical activity, and behavior therapy. Persons with obesity typically lose about 8 kg (approximately 8% of initial weight) with this approach, accompanied by improvements in health and quality of life.