The causes of obesity are complex. Like many human diseases and health conditions, obesity is the results of complicated interactions among genetic and environmental factors. On one end, there are many monogeneic obesity and obesity-associated genetic syndrome. However, they are often rare in incidence. These obesity disorders are usually inherited in Mendelian modes, like autosomal doimant, recessive or X-linked. Although obesity is an inherent features of these disorders, they are commonly presented with the other clinical pictures which are often quite severe physically and physiologically. The clinical courses of these disorders are not profoundly influenced by other environmental factors. In contrast to Medelian obesity, the other end of obesity spectrum is caused by polygenic model. Probably more than 200 genes have been implicated in producing obesity. However, the effect size of each gene is small and by itself can not induce significant weight gain. Accumulation of many obesity genes with a obesogenic environment is usually necessary. This is actually the cause of the common obesity in any modern society. In addition to the actions of the genes, epigenetics also play important roles revealed in recent years. Modulation of gene expression by many mechanisms including DNA methylation, histone modification, micro-RNA and long non-coding RNA all contribute to pathogenesis of obesity. Furthermore, the genomes of intestinal microbiota are also new fileds to dissect the etiology of common obesity in modern society.