Energy balance of the body is determined mainly by the function of various hypothalamic and brainstem nuclei, according to a complex interaction between the regulation of body temperature (actual metabolic rate vs. heat loss) and regulation of body weight (metabolic rate vs. food intake). The direct effect of central anabolic neuropeptides (neuropeptide Y, orexins, melanin concentrating hormone, etc.) is to enhance food intake and suppress metabolic rate with a tendency to cause hypothermia, while central catabolic neuropeptides (melanocortins, corticotropin releasing factor, cocaine-amphetamine regulated peptide, etc.) suppress food intake and enhance energy expenditure with a tendency to induce hyperthermia. Many other neuropeptides are neither clearly anabolic, nor clearly catabolic, but still influence these complex hypothalamic/brainstem functions. Some peripheral peptides (e.g. leptin, insulin, ghrelin) acting at either peripheral or cerebral sites also contribute to the regulation of energy balance. The prevailing thermoregulatory status, the substances or neural signals representing actual feeding vs. established nutritional states, and the aging process may modify the expression and/or activity of peripheral and central peptides and peptide receptors.