To stop or not to stop immunosuppressive therapy in the perioperative setting puts the clinician to a challenge. The risk of potential wound infection with possible septic or even lethal consequences needs to be weighted against exacerbation of the rheumatic disease. However, exacerbation of autoimmune inflammatory activity needs to be treated with increasing immunosuppressive medication, thus leading to enhanced risk of local and systemic infection as well. Unfortunately, up to now there is no data from randomized, double-blind controlled clinical trials available on how to steer immunosuppressive therapy in the perioperative setting, making evidence-based recommendations difficult. Neither is there good evidence, if the risk of infectious complications under immunosuppressive therapy differs according to the type and localization of surgery performed. Finally, immunosuppressive co-medication, like glucocorticoid dosage, is not adequately addressed in the available studies, making interpretation of these studies even more problematic. Therefore, a decision has to be made on an individual basis. We discuss the available data on DMARD and biologics therapy in the perioperative setting and describe our own perioperative management with different DMARDs and biologics.