Bariatric surgery is the most effective therapy for morbid obesity. Unfortunately, a significant number of patients experience significant postoperative weight regain, which undermines the metabolic and cardiovascular benefits of weight loss associated with surgery. When revisional procedures are not indicated and/or when behavioral factors are present (e.g., nonadherence, eating pathology), bariatric programs currently do not have any empirically evaluated treatment options to offer those burdened with less favorable outcomes. This chapter reviews the definition of successful weight loss after bariatric surgery, as well as some biologic and behavioral factors that could be implicated in weight regain after surgery. Finally, we outline the scientific evidence supporting the use of behavioral and medical therapies to prevent weight regain after surgery. Bariatric programs need to determine from clinical experience, as well as through clinical trials, what behavioral/medical therapies are the most effective for managing weight gain after bariatric surgery.