Obesity is a chronic disease. According to the repcrt of the World Health Organization, obesity is the most easily neglected disease currently, while its incidence is rapidly rising year after year. Monogenic obesity is a special one among all types of obesity because it is caused by the mutation of a single gene. With the development of molecular biology and many other technologies, a dozen of genes which play a critical role in monogenic obesity have been found now. In this paper, we reviewed these genes, their mutation sites, and the molecular pathogenic mechanism in monogenic obesity.