Human immunodeficiency type‐1 (HIV‐1) infection is known to cause disorders of the CNS, including HIV‐associated dementia (HAD). It is suspected that tumor necrosis factor‐α (TNF‐α) released by infected microglia and macrophages play a role in neuronal injury seen in HAD patients. Accordingly, studies suggest that the level of TNF‐α mRNA increases with increasing severity of dementia in patients, and that inhibitors of TNF‐α release reduces neuronal injury in murine model of HAD. However, the exact role of TNF‐α in relation to neuronal dysfunction is a matter of ongoing debate. One school of thought hails TNF‐α as the inducer and mediator of neurodegeneration and their evidence suggest that TNF‐α kill neurons directly by recruiting caspases or may kill indirectly by various means. In sharp contrast to this, another concept theory envisages a role for TNF‐α in negotiating neuroprotection during HAD. The current compilation examines these contradictory concepts, and evaluates their efficacy in the light of TNF‐α signaling. It also attempts to elaborate the current consensus outlook of TNF‐α's role during HAD.