This chapter presents the current state of knowledge in the field of the genetics of human obesity. The molecular approach has proved to be powerful in defining new syndromes associated with obesity. The pivotal role of leptin and melanocortin pathways has been recognized, but only in rare cases of obesity. In the more common form of obesity a multitude of polymorphisms located in genes and candidate regions throughout the genome regulate an individual's susceptibility to weight gain in a permissive environment. The effects are often uncertain and the results not always confirmed. Combining these single nucleotide polymorphisms and defining the associated risks for obesity will be a real challenge in the future. It is now necessary to integrate data of various origins (environment, genotype, expression) to clarify this field.