The development of the anti-TNF therapies is a milestone in the therapy of rheumatic diseases. As in all new treatment opportunities it is of concern whether all potential undesired side effects have been evaluated within the clinical trials which have lead to approval of the drugs. Postmarketing experience and pharmacovigilance programs are necessary to determine the overall safety profile of the new agents. From the clinical trials and the practical experience of the first years we know that side effects have occurred in patients treated with anti-TNF agents. Sufficient knowledge about these partly specific side effects is critical for rheumatologists who treat their patients with these very effective biologic drugs.