The widespread interest in Tumor Necrosis Factor (TNF) in biology and medicine is reflected in the hundreds of papers published every year on its regulation and actions. Many excellent reviews that consider various aspects of the biology of TNF have been published. This chapter summarizes the biology, regulation, and actions of TNF, with primary emphasis on the information available in food and companion animal species. The two primary methods of quantifying TNF are bioassays and immunoassays. The regulation of TNF activity is complex, befitting its potent effects in animals, the variety of conditions under which it is produced, and the range of functions and processes it modulates. The structure of the TNF gene has been examined in detail to elucidate the molecular basis of regulation at the transcriptional level. The induction and regulation of TNF expression in animals is assumed to be similar to that described above in humans and mice.