Infectious complications are a central problem in the treatment of patients with rheumatic diseases. The increased infection rate is mainly caused by immunosuppressive medication, particularly glucocorticoids. A more aggressive diagnostic approach, often including bronchoscopic procedures, is often necessary to obtain samples for microbiological examinations. In immuno-compromised patients the failure of a calculated empiric antibiotic therapy is associated with a higher risk of fatal outcome. Among possible opportunistic infections Pneumocystis jirovecii pneumonia (PCP), invasive aspergillosis and CMV reactivations are most relevant. Furthermore, particularly with the use of TNF-blocking agents, reactivation of latent tuberculosis (TB) might be observed. There are only a few situations in which anti-infective chemo-prophylaxis is established: In the case of latent TB INH-prophylaxis should be given when anti-TNF-therapy is considered. There is evidence in favour of PCP prophylaxis with trimethoprim/cotrimoxazole in patients receiving intense immunosuppression with high dose glucocorticoids and cyclophosphamide.