Obesity and its metabolic complications are major health problems in the United States and worldwide, and increasing evidence implicates the microbiota in these important health issues. Indeed, it appears that the microbiota function much like a metabolic “organ,” influencing nutrient acquisition, energy homeostasis, and, ultimately, the control of body weight. Moreover, alterations in gut microbiota, increased intestinal permeability, and metabolic endotoxemia likely play a role in the development of a chronic low‐grade inflammatory state in the host that contributes to the development of obesity and associated chronic metabolic diseases such as nonalcoholic fatty liver disease. Supporting these concepts are the observations that increased gut permeability, low‐grade endotoxemia, and fatty liver are observed in animal models of obesity caused by either high‐fat or high‐fructose feeding. Consistent with these observations, germ‐free mice are protected from obesity and many forms of liver injury. Last, many agents that affect gut flora/permeability, such as probiotics/prebiotics, also appear to affect obesity and certain forms of liver injury in animal model systems. Here the authors review the role of the gut microbiota and metabolic endotoxemia‐induced inflammation in the development of obesity and liver injury, with special reference to the intensive care unit setting.