The epidemic of obesity is developing faster than the scientific understanding of an efficient way to overcome it, as reflected by the low success rate of short- and long-term weight loss interventions. From a clinical standpoint, this suggests that the body tends to defend a set point of possible genetic origin in the context of a weight-reducing program. As described in this paper, this limited therapeutic success may depend on adaptive thermogenesis, which represents in this case the decrease in energy expenditure (EE) beyond what could be predicted from the changes in fat mass or fat-free mass under conditions of standardized physical activity in response to a decrease in energy intake. This issue has been documented in recent studies that have shown in obese individuals adhering to a weight reduction program a greater than predicted decrease in EE, which in some cases was quantitatively sufficient to overcome the prescribed energy restriction, suggesting a role for adaptive thermogenesis in unsuccessful weight loss interventions and reduced body weight maintenance. As also discussed in this paper, this 'adaptive thermogenesis' can be influenced by environmental factors, which have not been frequently considered up to now. This is potentially the case for plasma organochlorine concentration and oxygen desaturation in obstructive sleep apnea syndrome. It is concluded that health professionals should be aware that in some vulnerable individuals, adaptive thermogenesis can be multi-causal, and has the capacity to compensate, at least partly, for the prescribed energy deficit, possibly going beyond any good compliance of some patients.