It is well established that anti-tumor necrosis factor-⍺ (TNF⍺) antibody is an efficacious disease-modifying drug for rheumatoid arthritis and Crohn’s disease. Unfortunately, its long-term use can be associated with ominous pulmonary adverse events, most notably mycobacterial and fungal lung infections. To this end, reactivation of latent tuberculosis infection represents a serious concern of anti-TNF⍺ antibody therapy. Given the anticipated increase in the approved indications for these drugs, community-based physicians should be made aware of these events for implementation of better patient selection for anti-TNF⍺ antibody therapy and initiation of appropriate measures once these adverse events are observed. This review will address this issue by outlining: 1) the role of TNF⍺ in host inflammatory response to injury, particularly during mycobacterial and fungal infections; 2) the salutary effects of anti-TNF⍺ antibody therapy in human diseases; and 3) the ominous pulmonary adverse events associated with these drugs.