The development of obesity, a condition facilitated by the avalibility and increasing consumption of high caloric food and beverages as well as a general decrease in physical activity, has become a rapidly increasing health problem. Obesity and overweight increases the risk for developing diseases that shorten life, including type 2 diabetes, coronary heart disease, hypertension and cancer. Progress in understanding the precise and powerful biological mechanisms that maintains body weight within a relatively narrow range is crucial for future therapeutic strategies that may help to prevent and treat obesity. Over the past two decades, major advances have been made to clarify the neuronal pathways, chemical mediators and signal transduction mechanisms, which contribute to the process of energy homeostasis. A primary central nervous site for control of energy balance is the hypothalamus. Several peripheral tissues produce peptides/hormones that act via the brain, the arcuate nucleus in particular, to regulate short- and long-term food intake and energy expenditure. At least 25 transmitters have been suggested to play key roles in feeding behavior. During the last two decades attention has been focused on the role of different neuropeptides in hypothalamic control of feeding behavior. Some of the transmitter molecules that influence feeding behavior and which are produced in hypothalamic cell bodies will be reviewed, with special emphasis on GABA and glutamate, two relatively neglected regulators of energy balance. Hypothalamic transmitter molecules that participate in the control of ingestive behavior are primarily produced in neuronal cell bodies of the arcuate nucleus and/or the lateral hypothalamic area. These neurons send projections to a large number of regions of the central nervous system. Apart from producing orexigenic or anorexigenic compounds of peptidergic nature, the hypothalamic neurons also produce excitatory and inhibitory amino acid neurotransmitters. The role of GABA and glutamate in regulating energy balance have received less attention in comparison to neuropeptides. The arcuate nucleus-median eminence area, a region with a weak blood-brain barrier, contains at least two neuronal cell populations that extert opposing actions on energy balance. The majority of the neurons located in the ventromedial aspect of the arcuate nucleus, which produce the orexigenic peptides neuropeptide Y (NPY) and agouti-related peptide (AGRP), contain in addition the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD) and the vesicular GABA transporter (VGAT), thereby supporting their GABAergic nature. Some neurons producing pro-opiomelanocortin (POMC)- and cocaine- and amphetamine-regulated transcript (CART), located in the ventrolateral division of the arcuate nucleus have recently been reported to contain the vesicular glutamate transporter 2 (VGLUT2), a marker for glutamatergic neurons. In the lateral hypothalamic area, hypocretin/orexin neurons express VGLUT1 or VGLUT2, but not GAD, whereas some melanin-concentrating hormone (MCH) cells contain GAD. These observations support the view that GABA and glutamate, two relatively neglected feeding transmitters candidates, are present in key neurons that regulate body weight and consequently represent important orexigenic/anorexigenic mediators that convey information to other neurons within the hypothalamus as well as from the hypothalamus to other brain regions that participate in regulation of energy balance.