There is an asymmetry in the operation of physiological processes that maintain body weight. The body exerts a strong defence against undernutrition and weight loss, but applies a much weaker resistance to overconsumption and weight gain. These principles influence how appetite control operates and this constitutes one form of vulnerability to weight gain. The expression of appetite is reflected in an episodic pattern of eating behaviour, the selection of dietary commodities and an associated profile of conscious sensations such as hunger, preferences, aversions and fullness. The onset and termination of eating episodes are subject to facilitatory and inhibitory physiological processes, and are held in place by strong environmental contingencies and habitual routines. Energy intake resulting from physiological and environmental control of behaviour is generally in balance with energy expenditure, although changes in energy expenditure do not inevitably trigger changes in food intake. Excess energy intake over expenditure may be due to aberrant positive drive to seek energy or a permissive response to strong external stimuli. The former could arise from a defect in a lipostatic regulatory system, and the latter from the weakness of inhibitory signals or from strong facilitatory responses to superpotent physical features of food. Taste and textural qualities of food give rise to hedonic responses via opioidergic and aminergic systems. Inhibitory responses to macronutrients include adjustment of gastric volume, rate of gastric emptying, release of cholecystokinin and enterostatin, and changes in plasma levels of products of digestion. These peripheral responses lead to a series of changes in brain neurotransmitter networks. Proteins, fats and carbohydrates generate different sets of physiological responses that produce different effects on the intensity and duration of satiety. The nutrient composition of food and the overall energy density influence control of meal size and post-ingestive inhibition. Particular sensory and nutrient combinations in foods can facilitate passive overconsumption. Overriding physiological satiety signals can lead to a positive energy balance and weight gain.