The dual center hypothesis in the central control of energy balance originates from the first observations performed more than 5 decades ago with brain lesioning and stimulation experiments. On the basis of these studies the "satiety center" was located in the ventromedial hypothalamic nucleus, since lesions of this region caused overfeeding and excessive weight gain, while its electrical stimulation suppressed eating. On the contrary, lesioning or stimulation of the lateral hypothalamus elicited the opposite set of responses, thus leading to the conclusion that this area represented the "feeding center". The subsequent expansion of our knowledge of specific neuronal subpopulations involved in energy homeostasis has replaced the notion of specific "centers" controlling energy balance with that of discrete neuronal pathways fully integrated in a more complex neuronal network. The advancement of our knowledge on the anatomical structure and the function of the hypothalamic regions reveals the great complexity of this system. Given the aim of this review, we will focus on the major structures involved in the control of energy balance.