The carotid bodies (CBs) are peripheral chemoreceptors, classically defined as O2 sensors, but now looked as metabolic sensors involved in carbohydrates and lipid metabolism. Recently, we demonstrated that CBs activity is increased in metabolic disease animals and in prediabetic patients and that the resection of the carotid sinus nerve (CSN), the nerve that links the CB to the brain, prevented and reversed the metabolic alterations induced by hypercaloric diets. Also, CSN resection normalized the sympathoadrenal overactivity present in dysmetabolic states, meaning that the beneficial effects of decreasing CB activity are modulated by target-related efferent sympathetic nerves, through a reflex initiated in the CBs. Insulin, leptin, GLP1 and pro-inflammatory cytokines activate the CB. The present talk will provide a state-of-the-art update on the mechanisms of chemosensory transduction, neural circuitry, and reflex regulation of CBs chemoreceptor in metabolic diseases and will discuss the recent findings that disclose the brain regions involved in CB-dependent metabolic control to complete the circuit between CB-brain-peripheral tissues in the scenario of metabolic disorders.