During the past decades, obesity has become a major health problem worldwide. Balance of energy homeostasis is one of the most vital functions exerted by animals, and a very complex network of central and peripheral signaling systems is involved in its regulation. Recently, the cannabinoid receptor type 1 (CB1) and the endogenous cannabinoid system emerged as very important components for the control of energy balance. This system is proposed to regulate feeding behavior both at central and peripheral levels. In particular, the endogenous cannabinoid system is under the control of peripheral signaling systems such as leptin in the hypothalamus and might, in turn, regulate the action of hypothalamic feeding-regulatory neuropeptides. Endocannabinoids have also been proposed to participate in the rewarding properties of food in mesolimbic circuits of the brain. Moreover, the endogenous cannabinoid system regulates food intake in the gastrointestinal tract, possibly by modulating peripheral neuronal and hormonal responses to changes in feeding status. The main goal of this review is to highlight the most recent advances and concepts regarding the role of the endogenous cannabinoid system in control of energy balance and to discuss the prospectives for the use of CB1 antagonists in the therapy of obesity.