This paper reviews the current evidence for the role of antirheumatic therapy in the development of serious infections in patients with rheumatoid arthritis (RA). Prednisone is clearly associated with increased infectious risk, but no definitive data link methotrexate to infection. Emerging data suggest that biological agents also pose increase infectious risk, particularly when used in combination with corticosteroids or methotrexate. Further research is needed in this important aspect of RA treatment. In the meantime, the author recommends that physicians should remain vigilant for serious infections in their patients with RA and use appropriate vaccines and screening procedures to mitigate their risk.