In view of the exponential rise of global obesity in the past three quarters of the century, it is useful to examine what is driving this change and what approaches can curb it. The chief drivers of weight gain are, on one hand our misunderstanding of the mechanisms controlling energy balance, and, on the other, reliance on current, potentially misleading conflicting scientific opinions and government policies regarding the controls of human appetite. This review outlines the evidence that: (1) there is no direct bioenergetic feedback from energy metabolism or energy stores to the brain mechanisms guiding feeding and energy expenditure, (2) human appetite is controlled by signals originating from an empty or full stomach, food palatability and opportunities to eat as well by the rate of food absorption, that (3) humans bear a genetic burden of having high ability and capacity to store fat and mechanisms that curb body- mass and fat loss, (4) humans are motivated to overconsume while maintaining low energy expenditure, and (5) commercial interests of food businesses marketing highly palatable foods, and wide-spread mechanization of living tasks and urban design reduce the need for physical work and movement. The non-pharmacological and non-surgical solutions to obesity involve an understanding of human genetic impediments and environmental obstacles to maintaining healthy weight, coupled with deliberate corrective or preventive behaviors, such as understanding and using gastrointestinal tract signals that provide sufficient, albeit subtle, cues for sensible food intake, and using daily weight monitoring and activity tracking devices to record and motivate healthy levels of physical activity.