The prevalence of obesity is steadily rising and has huge health and financial implications for society. Weight gain is due to an imbalance between dietary intake and energy expenditure and research has focused on trying to understand the complex pathways involved in controlling these aspects. This review highlights the key areas of research in the hypothalamic control of appetite. The hypothalamus consists of several nuclei that integrate peripheral signals, such as adiposity and caloric intake, to regulate important pathways within the CNS controlling food intake. The best characterized pathways are the orexigenic neuropeptide Y/Agouti-related protein and the anorexigenic pro-opiomelanocortin/cocaine- and amphetamine-related transcript neurons in the arcuate nucleus of the hypothalamus. These project from the arcuate nucleus to other key hypothalamic nuclei, such as the paraventricular, dorsomedial, ventromedial and lateral hypothalamic nuclei. There are also projections to and from the brainstem, cortical areas and reward pathways, all of which influence food intake. The challenge at present is to understand the complexity of these pathways and try to find ways of modulating them in order to find potential therapeutic targets.