In the past two decades, two major discoveries have greatly contributed to our current knowledge on the central control of food intake and body-weight; the discovery of the anorexigenic adipocyte derived hormone leptin in 1994 and the orexigenic gut derived hormone ghrelin in 1999. Both hormones act as crucial signals to indicate nutritional status as well as to modulate feeding behaviour through a variety of distinct pathways. They target overlapping CNS regions in order to mediate their obvious opposing effects on energy balance. Here we depict the integral picture of leptin and ghrelin on central regulation of food intake by reviewing their actions across the CNS, in regions of the hypothalamus, brainstem, mesolimbic reward pathway and other higher brain areas.