Thermogenesis or facultative heat production is a fundamental process of the human body to respond to overnutrition and undernutrition in an attempt to maintain a constant lean body mass. In this process the sympathetic nervous system (SNS) is an important regulator of metabolic processes. Variations in energy intake and energy expenditure through exercise cause changes in SNS aimed to maintain energy homeostasis. Studies have shown that acute energy restriction leads to a reduction of the sympathoadrenal drive, resulting in a reduced thermogenic response. Overfeeding increases SNS activity, expending the surplus energy by accelerating metabolism. When the SNS is stimulated, all types of adrenoreceptors are activated, but thermogenesis is primarily mediated by both beta 1-adrenoreceptors and beta 2-adrenoreceptors. Response to energy restriction also results in modulation of the adrenergic receptor number and sensitivity. Comparing lean and obese individuals there is increasing evidence that in the obese the adaptive responsiveness of the SNS to changing energy status is blunted. The increased activation of SNS to respond adequately on the altered substrate demands during acute and prolonged physical exercise (training) is accompanied with an increase of resting metabolic rate (RMR) and lipid oxidation. The higher level of lipid oxidation at the same relative intensity of exercise is probably fueled by increased lipolysis of muscle triglycerides. Therefore, exercise may play an important role to overcome the impaired lipid oxidation in muscle of obese individuals, as was demonstrated in a number of studies.