TNF blockers have been available to treat various inflammatory disorders since more than a decade. T cells and macrophages mainly express TNF and activate many cells through two types of receptors. Pharmaceutical companies developed two types of TNF blockers: soluble receptors and monoclonal antibodies. Understanding of differences of structure and function can explain divergence of efficacy or side effects. Etanercept has the best retention rate in rheumatic diseases, but is less or not effective in granulomatous diseases, such as inflammatory bowel diseases or uveitis. However, etanercept induces less tuberculosis infections than anti-TNF blocker monoclonal antibodies.