Type 2 diabetes is associated with obesity and is increasing at an alarming rate in youth. Although weight loss through lifestyle change is one of the primary treatment recommendations for adults with type 2 diabetes, the efficacy of this approach has not been tested with youth. This paper provides a summary of the reviews and meta-analyses of pediatric weight-loss interventions that informed the design and implementation of an intensive, family-based lifestyle weight management program for adolescents with type 2 diabetes and their families developed for the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. A total of 1092 youth have been screened, and 704 families have been randomized for inclusion in this 15-center clinical trial sponsored by the National Institutes of Health. The TODAY study is designed to test three approaches (metformin, metformin plus rosiglitazone and metformin plus an intensive lifestyle intervention) to the treatment of a diverse cohort of youth, 10-17 years of age, within 2 years of their diagnosis. The principal goal of the TODAY Lifestyle Program (TLP) is to decrease baseline weight of youth by 7-10% (or the equivalent for children who are growing in height) through changes in eating and physical activity habits, and to sustain these changes through ongoing treatment contact. The TLP is implemented by interventionists called Personal Activity and Nutrition Leaders (PALs) and delivered to youth with type 2 diabetes, and at least one family support person. The TLP provides a model for taking a comprehensive, continuous care approach to the treatment of severe overweight in youth with comorbid medical conditions such as type 2 diabetes.