In mammals and birds, conservation of body heat at around 37 °C is vital to life. Thermogenesis is the production of this heat which can be obligatory, as in basal metabolic rate, or it can be facultative such as the response to cold. A complex regulatory system has evolved which senses environmental or core temperature and integrates this information in hypothalamic regions such as the preoptic area and dorsomedial hypothalamus. These areas then send the appropriate signals to generate and conserve heat (or dissipate it). In this review, the importance of the sympathetic nervous system is discussed in relation to its role in basal metabolic rate and adaptive thermogenesis with a particular emphasis to human obesity. The efferent sympathetic pathway does not uniformly act on all tissues; different tissues can receive different levels of sympathetic drive at the same time. This is an important concept in the discussion of the pharmacotherapy of obesity. Despite decades of work the medicine chest contains only one pill for the long term treatment of obesity, orlistat, a lipase inhibitor that prevents the absorption of lipid from the gut and is itself not systemically absorbed. The central controlling system for thermogenesis has many potential intervention points. Several drugs, previously marketed, awaiting approval or in the earlier stages of development may have a thermogenic effect via activation of the sympathetic nervous system at some point in the thermoregulatory circuit and are discussed in this review. If the balance is weighted to the "wrong" side there is the burden of increased cardiovascular risk while a shift to the "right" side, if possible, will afford a thermogenic benefit that is conducive to weight loss maintenance. This article is part of a Special Issue entitled 'Central Control Food Intake'