The new lifestyle in the modern world is causing a rapid increase in the prevalence of obesity and associated health problems. Increased availability of palatable and energy dense foods, combined with a lack of physical activity overpower a homeostatic regulatory system that evolved to survive periods of famine rather than preventing obesity. Environmental and lifestyle factors influence energy balance mainly through their impact on cortico-limbic brain structures dealing with reward, cognitive, and social aspects of food intake and voluntary physical activity. To find new behavioral and pharmacological treatments of obesity, it will be important to identify the specific pathways that link these externally driven processes with the homeostatic regulatory system.