Tumor necrosis factor (TNF) antagonists are drugs developed to block endogenous TNF, an essential proinflammatory molecule with a central role in the pathogenesis of rheumatoid arthritis (RA). Although extensive studies have been performed concerning the mode of action of TNF-blocking agents, there are still many unresolved questions and potential differences between different TNF-blocking drugs. One unresolved issue is to what extent apoptosis is affected by TNF blockade in RA. We provide an overview of studies that have investigated the proapoptotic effect of different anti-TNF drugs in RA, searching for a unified interpretation of somewhat contradictory data.