Tumor necrosis factor alpha (TNFα) is a prototypic ligand of the TNF superfamily. It is a versatile cytokine that plays a central role in inflammation, immune system development, apoptosis, and lipid metabolism. TNFα is an important endogenous pyrogen, its release quickly induces fever. It also causes apoptotic cell death, cachexia, inflammation, and has the ability to inhibit tumorigenesis and viral replication. It is chemoattractive to many immune cells, particularly neutrophils. Cell surface TNFα can induce the lysis of neighboring tumor cells and virus infected cells and has the ability to generate its own downstream cell signaling. It is produced chiefly by activated macrophages, although it is produced in low levels by a wide variety of immune, epithelial, endothelial, and tumor cells such as CD4+ lymphocytes, NK cells, neutrophils, mast cells, eosinophils, and neurons. TNFα also plays an important role in metabolism, with the ability to induce insulin resistance and regulate appetite through interactions with the hypothalamus. Dysregulation of TNF production has been implicated in a variety of human diseases including Alzheimer’s disease, inflammatory bowel disease, arthritis, cancer, and psoriasis.