Patients with rheumatoid arthritis (RA) has an increased infections risk and morbidity and mortality related to infections. This increased risk may occur due to the disease itself with intrinsic cellular immunity alterations or as a results of drugs used to control the disease. The potential risk of infections related to conventional disease modifying anti-rheumatic drugs (DMARDs) is not completely clarified. Methotrexate (MTX) may increase the infectious risk, but its positive effect on disease activity results in a reduction of further risk factors for infections. Data about the increased risk of pneumonia or reactivation of silent infection remain controversial. Leflunomide (LEF) seems safe in controlled trial even if it has been associated with the onset of infections requiring hospitalization, such as pneumonia. Data about other DMARDs are scanty and the main cause of interruption of therapy is related to toxicity different from infection. Beside the general positive profile of DMARDs as for infectious risk, a careful use and tight control of the patients is recommended.