Corticosteroids and cytotoxic drugs form the conventional immunomodulators in rheumatology. This therapeutic arsenal has recently been widened by TNF-alpha antagonists and other anti-cytokines. If rheumatoid arthritis is itself associated with infections, immunomodulating therapies further increase the risk of infection, especially when used in combination therapies. Among conventional therapies, corticosteroids are associated with the highest risk for both common bacterial and opportunistic infections. Infliximab is the TNF-alpha antagonist associated with the highest risk of infection. Its use has been particularly associated with cases of severe tuberculosis. All patients at risk for tuberculosis, treated with corticosteroids or TNF-alpha antagonists, should therefore receive an adequate prophylaxis.