Tumor necrosis factor (TNF) is a multifunctional cytokine which has excited and fascinated numerous investigators and commercial entities due to its promise as a therapeutic agent against cancer and as a target for drugs treating septic shock. TNF is a protein having cytotoxic, cytostatic, immunomodulatory as well as several other activities and is also involved in septic shock. This review covers the structure of TNF and its receptors, various in vitro activities and in vivo activities based on studies in animal model systems. The role of TNF as an anticancer therapeutic agent, based on various phase I and phase II clinical studies, has also been considered. The review concludes with several considerations for increasing the therapeutic utility of TNF in terms of targeting, toxicity and half-life.