Because of the enduring rise in the prevalence of obesity worldwide, there is continued interest in hypoxia as a mechanism underlying the pathophysiology of obesity and its comorbidities and as a potential therapeutic adjunct for the management of the disease. Lifelong exposure to altitude is accompanied by a lower risk for obesity, whereas altitude sojourns are generally associated with a loss of body mass. A negative energy balance upon exposure to hypoxia can be due to a combination of changes in determinants of energy expenditure (resting metabolic rate and physical activity energy expenditure) and energy intake (appetite). Over the past 15 years, the potential therapeutic interest of hypobaric or normobaric hypoxic exposure in individuals with obesity-to lower body mass and improve health status-has become an active field of research. Various protocols have been implemented, using actual altitude sojourns or intermittent normobaric hypoxic exposures, at rest or in association with physical activity. Although several studies suggest benefits on body mass and cardiovascular and metabolic variables, further investigations are required before recommending hypoxic exposure in obesity management programs. Future studies should also better clarify the effects of hypoxia on appetite, the intestinal microbiota, and finally on overall energy balance.