Recent advances in understanding the monogenic forms of human obesity have occurred at a rapid rate. Although rare, congenital leptin deficiency is now recognized as a treatable form of severe obesity. Mutations in the melanocortin 4 receptor are responsible for up to 6 % of cases of early-onset severe childhood obesity. We are also gaining increasing understanding of the mechanisms of obesity associated with mutations in pro-opiomelanocortin, prohormone convertase 1 and the leptin receptor. In addition, the genes underlying several forms of the Bardet-Biedl syndrome and that responsible for Alstrom syndrome have recently been cloned. In the case of these complex pleiotropic syndromes, the link between the precise gene involved in the obese phenotype is still obscure. In parallel with other human quantitative disorder, such as those affecting blood pressure and plasma glucose, dissecting the genetic basis for common obesity has been much more challenging. However, several genome-wide scans have provided applicated evidence for the involvement of particular chromosomal regions and it is only a matter of time before the genetic variants in those regions contributing to human variation in body fat mass will be identified.