Tumor necrosis factor (TNF-alpha) plays an essential role in the orchestration of inflammatory processes including autoimmune disorders, host defence and granuloma formation. TNF antagonists are highly effective in the therapy of rheumatoid arthritis, but they compromise host defence mechanisms, especially concerning bacterial infections inducing granuloma formation, such as tuberculosis. Other biologics have been developed and approved for the therapy of rheumatoid arthritis, e.g. an interleukin (IL-1) blocking agent (anakinra), an antibody that depletes CD20 positive B-cells (rituximab) and an inhibitor of T-cell co-stimulation (abatacept). In spite of initial skepticism regarding side effects, such as an increased risk of infections, biologics now play an essential role in the therapy of autoimmune diseases due to the implementation of efficient screening measures concerning side effects (such as reactivation of tuberculosis). This review summarizes the current available data regarding risk of infection and gives and overview on recommended screening, contraindications and events that require withdrawal of therapy.