The role of the endocannabinoid system in the regulation of appetite in children. Appetite regulation is complex and depends on multiple complex inter-relationships involving hormonal, peripheral and central signals. The endocannabinoid system (ECS) is one of the many factors involved. This system is important in regulating appetite in response to the availability of energy and nutrients and mediates the anorexigenic and orexigenic effects of exogenous cannabinoids. It also plays a significant role in regulating satiety and feelings of fullness. However, there have been few studies investigating the effect of endocannabinoid deficiency or activation on appetite in humans. Human studies have reported that the ECS is an important modulator of appetite under normal and pathophysiological conditions. Specifically, an imbalance between the satiating effects of the endocannabinoids anandamide and 2-arachidonoylglycerol, as opposed to their orexigenic effects on hunger signalling, may contribute to an overweight condition. In addition, the cannabinoid receptor agonists rimonabant and cannabidiol have been reported to decrease appetite in some studies. The ability of the ECS to influence appetite under the influence of macronutrients, and dietary habits, needs to be further investigated. Obesity may represent a developmental endocannabinoid deficiency and may have genetic implications. This review focuses on data collected from human studies investigating the role of the ECS in the modulation of appetite in children.