The metabolic syndrome, a cluster of risk factors for cardiovascular disease, is closely related to environmental and lifestyle risk factors. Increasing evidence suggests that environmental risk factors may involve an increase in xenobiotic exposure, for example due to environmental toxins, medications, high meat intake, food additives and supplements; while lifestyle risk factors, such as sedentary lifestyles, may involve a decrease in the detoxification and elimination of xenobiotics. The skin, the body's largest organ, plays a distinct role in the detoxification and elimination of xenobiotics and the body lipid homeostasis, which is affected by sedentary lifestyle and physical activity, as well as by ambient temperature. Thus, it seems that decreased skin biotransformation and excretion, for example due to low ambient temperature and sedentary lifestyle, may be an important risk factor for metabolic syndrome. This review aims to provide insight into the role of the skin in the development of metabolic syndrome.