Energy balance is a key concept in the etiology and prevalence of obesity and its co-morbidities, as well as in the development of possible treatments. If energy intake exceeds energy expenditure, a positive energy balance develops and the risk for overweight, obesity, and its co-morbidities increases. Energy balance is determined by energy homeostasis, and challenged by sensitivity to food reward, and to modulatory factors such as circadian misalignment, high altitude, environmental temperature, and physical activity. Food reward and circadian misalignment increase the risk for overweight and obesity, while high altitude, changes in environmental temperature, or physical activity modulate energy balance in different directions. Modulations by hypobaric hypoxia, lowering environmental temperature, or increasing physical activity have been hypothesized to contribute to body weight loss and management, yet no clear evidence has been shown. Dietary approach as part of a lifestyle approach for body weight management should imply reduction of energy intake including control of food reward, thereby sustaining satiety and fat free body mass, sustaining energy expenditure. Green tea catechins and capsaicin in red pepper in part meet these requirements by sustaining energy expenditure and increasing fat oxidation, while capsaicin also suppresses hunger and food intake. Protein intake of at least 0,8 g/kg body weight meets these requirements in that it, during decreased energy intake, increases food intake control including control of food reward, and counteracts adaptive thermogenesis. Prevention of overweight and obesity is underscored by dietary restraint, implying control of sensitivity to challenges to energy balance such as food reward and circadian misalignment. Treatment of overweight and obesity may be possible using a medium-high protein diet (0,8-1,2 g/kg), together with increased dietary restraint, while controlling challenges to energy balance.