The prevalence of obesity is rising to epidemic proportions in many countries worldwide. Obesity seriously increases an individuals risk of developing many health problems including diabetes. Diabetes, like obesity, is also in epidemic proportions with 300 million adults predicted to have the disease by 2025. Investigating strategies for the prevention and treatment of obesity and diabetes is vitally important. Autonomic dysfunction is evident in both obesity and diabetes. In persons with diabetes, impaired cardiovascular autonomic activity is characterized by a reduction in parasympathetic tone with a relative increase in sympathetic activity and is specifically associated with a number of clinically significant manifestations including exercise intolerance, intraoperative cardiovascular lability, orthostatic hypotension, silent myocardial ischemia, and increased risk of mortality. In obesity, parasympathetic function is decreased while regional heterogeneity of increased sympathetic activity may occur. Autonomic dysfunction increases cardiovascular workload, hemodynamic stress, serious dysrhythmias, and significant cardiac pathology. Thus, cardiac autonomic imbalance may also be an important link between obesity and increased morbidity and mortality. Beyond the obese and diabetic state, multiple variables associated with these conditions such as insulin, glucose, leptin, adiponectin and free fatty acids have an affect on the autonomic nervous system. Autonomic disturbances, however, appear to be reversible with weight reduction. Since autonomic imbalance is a marker of adverse risk, improvement obtained from weight loss should be beneficial for the health of individuals with obesity and diabetes. This overview will examine the relationship of the autonomic nervous system in obesity and diabetes and explore the effect of weight loss on autonomic function.