The notion of regulation is key to the understanding of body weight control. The independent life of animals requires the active regulation of many critical parameters of the internal status of the organism, i.e., their maintenance within a narrow range of defended values. Food intake is not one of such parameters. Food intake is one of many effector mechanisms that contribute to the regulation of several internal parameters, such as glycemia and adipose stores. The science of the last century has clarified the fine machinery of regulatory processes. Beyond the early notion of feedback loops triggering regulatory responses to existing need states, it is now recognized that efficient regulation rests on learned anticipatory responses, both physiological and behavioral, that are highly plastic and continuously shaped by the experience of environmental conditions. In humans, a wide range of factors (genetic, psychological, sociocultural, environmental, etc.) exert a significant influence on eating patterns. In spite of the massive influence of environmental and social factors, regulatory adjustments can be detected in the food intake of humans, including persons with obesity. Impressive developments in knowledge have paralleled an unprecedented worldwide increase in the frequency of obesity. In this field, knowledge does not equate power. Even in the present obesogenic world, however, food intake matches energy needs perfectly in many individuals with healthy weight. Understanding why regulation mechanisms allow body adiposity to drift upward in so many others remains a crucial challenge.