Metabolic syndrome is associated with adverse health outcomes and is a growing problem worldwide. Although efforts to harmonise the definition of metabolic syndrome have helped to better understand the prevalence and the adverse outcomes associated with the disorder on a global scale, the mechanisms underpinning the metabolic changes that define it are incompletely understood. Accumulating evidence from laboratory and human studies suggests that activation of the sympathetic nervous system has an important role in metabolic syndrome. Indeed, treatment strategies commonly recommended for patients with metabolic syndrome, such as diet and exercise to induce weight loss, are associated with sympathetic inhibition. Pharmacological and device-based approaches to target activation of the sympathetic nervous system directly are available and have provided evidence to support the important part played by sympathetic regulation, particularly for blood pressure and glucose control. Preliminary evidence is encouraging, but whether therapeutically targeting sympathetic overactivity could help to prevent metabolic syndrome and attenuate its adverse outcomes remains to be determined.