Tumor necrosis factor alpha (TNF⍺) is a pro-inflammatory cytokine that plays pivotal roles in regulating the inflammatory response in rheumatoid arthritis (RA). Intensive studies on TNF⍺-driven inflammation processes have led to the development of TNF⍺ blockers for RA treatment. However, response to these therapies is heterogeneous with roughly two-thirds of patient response and one-third non-response. Given the destructive nature of RA, the risk of adverse effects, and considerable costs for TNF⍺ blocker therapy, there is a strong need to identify predictors of response prior to start the TNF⍺ blocker therapy. Here we review several studies focused on predicting the response to TNF⍺ blockers. Demographic, clinical, radiological, blood, genetic or synovial tissue biomarkers were studied to find some predictive biomarkers of TNF⍺ blocker response. Unfortunately, results from these studies are heterogeneous. Discrepancy between these studies can be explained in part to the heterogeneity between the studies. As difference in the response criteria used, the delay of efficacy for the primary endpoint, and the genetic background of each population were all observed. Nevertheless, a high local and systemic level of TNF⍺ prior to TNF⍺ blocker therapy seems to be associated with a good clinical response. However, to validate these results, additional studies using independent and large cohorts are needed.