Over the last 12 years, TNF antagonists have been successfully used for the treatment of numerous patients afflicted by chronic inflammatory disorders. However, data from clinical trials and registries have shown that patients treated with these biologics have an increased risk of reactivating latent TB. The fact that TNF plays a role in the immune cell response and, more specifically, in maintenance of granuloma integrity is the accepted grounds for reactivation of TB following inhibition of TNF. Appropriate screening of latent TB and proper management of cases substantially reduces the incidence of active TB. Nevertheless, debate still remains regarding the value of the tuberculin skin test and IFN-γ-release assays as diagnostic tools, and treatment across guidelines and recommendations. This largely reflects differences in background population.