The global increase in the prevalence of childhood obesity is attributed to major recent changes in the environment, although obesity risk is intrinsically associated with individual genetic variations. The investigation of the genetic basis of obesity allowed the identification of several genes associated with monogenic childhood obesity. This review summarises the state-of-the-art technology in this field, recapitulates a strategy for clinical genetic testing and the new emerging drugs for a better management of earlyonset severe forms of obesity.