In humans, the intestinal microflora is inherited from our parents and from the environment. It has established an ecological mutualism with the host, allowing each organism to benefit from the symbiotic relationship. Based on recent evidence, some molecular mechanisms for the role of intestinal microflora on the control of energy metabolism have been proposed. During metabolic diseases such as obesity and diabetes, it has been proposed that an imbalance between the two dominant groups of beneficial bacteria, the Bacteroidetes and the Firmicutes, generates signals controlling the expression of genes by the epithelial intestinal cells. Genes involved in lipid metabolism such as the Fast Induced Adipocyte Factor have been considered as putative targets. In addition, bacterial extracts such as the lipopolysaccharides control the tone of the innate immune system thus regulating the general inflammatory status, insulin resistance, and adipose tissue plasticity. Therefore, strategies aimed at controlling the ecological mutualism between intestinal microflora and the host should lead to a new era of therapeutic and health benefits.