O besity is a significant health challenge, with the latest projections estimating that there will be 2.16 billion overweight and 1.12 billion obese individuals globally by 2030. In addition to social stigmatization and impaired quality of life, obese people are faced with significantly increased risk of cardiovascular disease, type 2 diabetes mellitus, and a number of cancers. Weight gain results from a sustained imbalance between energy intake (calories consumed) and energy expenditure (calories burned), resulting in positive energy balance. To tip energy balance toward weight loss, not only should food intake be decreased, but increasing physical activity may help. It is important to realize, however, that the secular rises in obesity over the past 3 to 4 decades can be explained by both physiological and environmental drivers and a number of putative factors ( Figure 1). 1,2 At one level, the obesity epidemic is a classic gene-environment interaction in which the human genotype is susceptible to environmental influences that affect energy intake and expenditure, with the obesogenic environment being dominant. These environmental factors include the 2 obvious explanations, ie, reduced physical activity and increased energy intake from high-calorie food and drinks, with the latter likely being the dominant factor. 3 However, other less studied factors have been implicated, including longer time spent awake, increased mean age of mothers at first birth, decreased prevalence of smoking, presence of environmental pollutants, ingestion of many novel medications, and reduction in the variability of seasonal ambient temperature owing to the presence of almost ubiquitous air conditioning. 4 Fundamentally, the obesity epidemic is explained by a dysregulation of energy balance in our obesogenic environment. Understanding the cause of obesity requires the study of how genetic and environmental factors interact to produce long-term positive energy balance.As a consequence of the obesogenic environment, the treatment of obesity requires intensive lifestyle modification. However, lifestyle modification in obese individuals tends to provide only transient success, and pharmacological treatment of obesity has often been disappointing and is very contentious because of the many safety concerns. Other approaches such as bariatric surgery are costly and not without risk. Thus, there is a concerted effort to find novel strategies to reduce excess body weight. This includes the potential of increasing energy expenditure via the stimulation of brown adipose tissue (BAT), now known to be present in adult humans. We would expect that such physiological or pharmacological stimulation of thermogenesis (heat production) would lead to dissipation of at least some excess ingested calories. This review provides a historical overview on the research on BAT, highlights recent developments in the field, and concludes with a discussion of the relevant issues that need to be addressed before BAT is considered a therapeutic option for human obe...