Pediatric obesity is highly prevalent in developed countries globally (and worsening in developing countries) and threatens to shorten the lifespan of the current generation. At highest risk for weight-related comorbidities including Type 2 diabetes mellitus, non-alcoholic fatty liver disease and dyslipidemia is a sub-set of children with severe obesity, often defined as a body mass index (BMI) percentile ≥99th percentile for age and sex. The pathophysiology of severe obesity in childhood is complex, resulting from the dynamic interplay of a myriad of individual and societal factors including genetic predisposition and health behaviors contributing to energy imbalance. Approximately 4–6% of children have severe obesity, representing a common scenario encountered by providers, and intervention is critical to halt ongoing weight gain and, when possible, reverse the trend. Clinical approaches promoting behavioral weight loss may result in modest, albeit clinically significant, reductions in BMI; however, such changes are often difficult to maintain long-term. Data regarding the impact of targeted pharmacotherapy including agents such as orlistat are limited in the pediatric population and again only suggest modest results. However, increasing evidence suggest that surgical treatment, as an adjunct to ongoing lifestyle changes, may be a promising option in carefully-screened adolescents with severe obesity and weight-related comorbidities who are motivated to adhere to the long-term treatment needs.