The rising prevalence of childhood obesity is driven by factors that promote an increase in energy intake and factors that contribute to a decrease in energy expenditure such as sedentary lifestyles and reduced physical activity at school and in leisure time. As the number of children presenting for clinical assessment is increasing, pediatricians need a systematic approach to the assessment of severe childhood-onset obesity and to consider genetic causes. For the purposes of clinical assessment, it remains useful to categorize the genetic obesity syndromes as those with dysmorphism and/or developmental delay and those without these features, but the spectrum of clinical features can be quite variable. The diagnosis of a genetic obesity syndrome can provide information that has diagnostic value for the family to whom genetic counselling can be provided. A genetic diagnosis can inform management and can inform clinical decision-making regarding the use of bariatric surgery.