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Abstract The central nervous system (CNS) controls food intake and energy expenditure via tight co-ordinations between multiple neuronal populations. Specifically, two distinct neuronal populations exist in the arcuate nucleus of hypothalamus (ARH): the anorexigenic (appetite-suppressing) proopiomelanocortin (POMC) neurons and the orexigenic (appetite-increasing) neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons. Coordinated regulation of neuronal circuit involving these neurons is essential to properly maintain energy balance, and any disturbance therein may result in hyperphagia/obesity or hypophagia/starvation. Thus, adequate knowledge on the POMC and NPY/AgRP neuron physiology is mandatory to understand the pathophysiology of obesity and related metabolic diseases. This review will discuss the history and recent updates on the POMC and NPY/AgRP neuronal circuits as well as the general anorexigenic and orexigenic circuits in the CNS.