Tumor necrosis factor-α (TNFα) was discovered over two decades ago and has since been identified as a key regulator in various inflammatory diseases. TNFα is produced by macrophages and other immune cells and plays a crucial role in cell proliferation, survival, differentiation, and apoptosis. Abnormal TNFα production and signaling have been linked to diseases such as rheumatoid arthritis, Crohn’s disease, atherosclerosis, psoriasis, sepsis, diabetes, and obesity. TNFα signaling involves two transmembrane receptors, TNFR1 and TNFR2, which activate multiple signaling pathways, including NFκB, JNK, and p38 MAPK. Inflammation and disease processes are significantly influenced by TNFα, making it a therapeutic target. Anti-TNFα drugs, such as etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab, have been licensed for treating inflammatory conditions. These drugs block TNFα to reduce inflammation and improve patient outcomes. However, further research is needed to optimize therapeutic approaches and understand the complex mechanisms of TNFα signaling in different diseases.Tumor necrosis factor-α (TNFα) was discovered over two decades ago and has since been identified as a key regulator in various inflammatory diseases. TNFα is produced by macrophages and other immune cells and plays a crucial role in cell proliferation, survival, differentiation, and apoptosis. Abnormal TNFα production and signaling have been linked to diseases such as rheumatoid arthritis, Crohn’s disease, atherosclerosis, psoriasis, sepsis, diabetes, and obesity. TNFα signaling involves two transmembrane receptors, TNFR1 and TNFR2, which activate multiple signaling pathways, including NFκB, JNK, and p38 MAPK. Inflammation and disease processes are significantly influenced by TNFα, making it a therapeutic target. Anti-TNFα drugs, such as etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab, have been licensed for treating inflammatory conditions. These drugs block TNFα to reduce inflammation and improve patient outcomes. However, further research is needed to optimize therapeutic approaches and understand the complex mechanisms of TNFα signaling in different diseases.