The agricultural and technological revolutions of the late 20th century have influenced both of the discretionary components of the energy balance equation, namely energy intake and physical activity. These changes act synergistically in the direction of encouraging weight gain and represent an unprecedented change in man's ecological niche. Obesity is the predictable biologic response to these external changes. This paper reviews the physiologic responses to modern diets and their effect on energy regulation. The energy density of foods is identified as a key element in influencing energy intake due to weak satiety signals that fail to compensate for very energy-dense foods. Evidence is also presented to show that interactions between energy-dense diets and low-levels of physical activity are key elements in encouraging weight gain due to an asymmetry between the hunger and satiety arms of human appetite control