Rituximab (RTX), a mouse/human chimeric anti-CD20 IgG1 monoclonal antibody has been effectively used as a single agent or in combination with chemotherapy regimen to treat lymphoma since 1997. In addition, it has been used to treat idiopathic thrombocytopenic purpura, systemic lupus erythematous, rheumatoid arthritis, and autoimmune hemolytic anemia. Recently, RTX has also been suggested for the treatment of certain connective tissue disease-related interstitial lung diseases (ILD) and hypersensitivity pneumonitis. Rare but serious pulmonary adverse reactions are reported. To raise awareness about this serious side effect of RTX treatment, as the indication for its use increases with time, we report five cases of probable RTX-ILD and discuss the current literature on this potentially lethal association.