Excess adiposity is associated with increased incidence of cardiovascular disease (CVD). A key player linking CVD development and obesity is the sympathetic nervous system (SNS). While the cardiovascular effects of the SNS are well appreciated, the SNS also exerts a profound influence on metabolic function. Hence, alterations in SNS activity may play a role in the etiology and complications of obesity. Central obesity is the fundamental manifestation of the metabolic syndrome and is linked to the degree of sympathetic nervous activation in obesity. Additionally, insulin resistance, hypertriglyceridemia, reduced high-density lipoprotein cholesterol, hypertension and glucose intolerance, may exacerbate the development of CVD. Recent data from our group demonstrated that individuals with the metabolic syndrome display elevated SNS activity with the degree of activation being inversely related to their insulin sensitivity and individuals who are insulin resistant are characterised by a blunted sympathetically mediated thermogenic response to a meal, which may reduce the facultative thermogenesis and contribute to weight gain. Individuals with impaired cholesterol profile also display further SNS activation and endothelial dysfunction. Weight loss achieved by life style changes and bariatric surgery is associated with significant improvement of the metabolic profile and a profound reduction in SNS activity. Elevated SNS activity is also present in overweight individuals who are young and otherwise healthy and SNS activity is directly related to the degree of renal, endothelial and cardiac dysfunction. Targeting the SNS may be an attractive and important avenue for the treatment of obesity and associated metabolic disorders.