The burden of disease associated with the obesity epidemic shortens lives, and prevalence is accelerating. As with other chronic diseases, improved outcomes are associated with effective self-management of obesity across the life span. The disease of obesity, then, fits squarely within the disease management and chronic care models. This article reviews selected interventions, described in peer-reviewed literature, designed to achieve significant weight loss for individuals identified as overweight or obese. The study objective is to provide an overview of the full range of methods and models for weight loss, including some available without medical supervision. The intended audience includes individuals and organizations with an expressed interest in disease management and the chronic care models. Our review identified promising lines of investigation for future research that span diverse medical disciplines applied to obesity. The quality of the studies included in our review was uneven, and compromises the current evidence for effectiveness and efficacy. Generally, our results showed that combination approaches-surgical or pharmacologic, combined with a behavioral intervention-were most likely to be effective.