Understanding of the mechanisms involved in the control of food intake and regulation of energy balance has increased greatly in recent years, thanks in part to the discovery of leptin, an event that ushered in a renaissance in research in this field. Over the last 5 years, several other neuropeptides that affect food intake and energy balance have been discovered, including cocaine- and amphetamine-regulated transcript (CART), melanin-concentrating hormone (MCH), orexin/hypocretin, and agouti-related protein (AGRP). In addition, new roles have been defined for previously discovered factors, such as galanin and NPY, and the cytokines interleukin-1 (IL1) and tumor necrosis factor alpha (TNF"). These recent advances have been possible because of new technologies, including cloning, transgenics, genomics and bioinformatics. For example, positional cloning techniques have been used to identify the genes for these peptides and factors and their receptors. Knowledge about specific transcription factor binding motifs in promoter regions allows development of specific agents that alter gene expression. By using transgenic and cloning techniques, genes can be added or deleted, and transcription can be enhanced or suppressed to produce new animal models for studying interactions among factors. Over the next few years, the combination of microarray techniques and proteomics with sophisticated informatics tools will continue to provide fundamental insights into the complex physiological processes involved in feeding behavior and metabolism.