Tumour necrosis factor alpha (TNF-alpha) is an inflammatory cytokine primarily produced by macrophages. It is a unique protein with contradictive properties; it has the ability to induce cellular death by apoptosis and oncosis, but can also induce cellular regeneration and growth. Genetic polymorphisms in TNFA have been associated with poor outcome in some surgical patients and this may provide a useful tool to screen for high-risk patients. Manipulating TNF-alpha levels in vivo may influence the progression of several pathological conditions. TNF-alpha has anti-cancer properties and has been used to treat cancer patients. Treatment with anti-TNF-alpha drugs and antibodies has been successful in rheumatoid arthritis and other autoimmune diseases, but disappointing in the management of patients with sepsis. This review article focuses on the biological activities, genetic polymorphism of TNFA and the role of TNF-alpha and anti-TNF-alpha treatments, based on animal experiments and clinical trials.