Cognitive behavioral interventions have formed the cornerstone of obesity treatment for the past two decades. These techniques, often combined with diet and exercise strategies, have been shown to produce weight losses of sufficient magnitude so as to reduce health risks. Though success in producing short-term weight loss is improving, many factors, including a metabolic energy gap, continue to challenge long-term weight maintenance results. This article reviews the unique influence of cognitive, behavioral, and metabolic factors on weight loss and weight-loss maintenance, and how future treatment packages might be modified to improve long-term weight loss outcomes.