Despite substantial advances in the treatment of inflammatory rheumatic diseases, not all patients respond adequately to conventional, biological or targeted synthetic disease-modifying antirheumatic drugs (DMARD). In particular, in systemic diseases such as systemic sclerosis or systemic lupus erythematosus, disease progression can lead to irreversible organ damage and increased mortality. For these refractory patients, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) has been successfully used for the past 30 years. The available data suggest that by the elimination of autoreactive immunological memory and the resetting of the immune system drug-free remission is possible; however, this approach can be associated with substantial side effects, including the risk of transplantation-related mortality (TRM), which can substantially vary depending on the disease, treatment protocol and individual risk factors and is between 0% and 5% in currently available studies. The TRM can be minimized by careful patient selection, treatment by a qualified multidisciplinary team and standardized treatment and monitoring protocols. This review article presents the current state of research and the results of an updated recommendation of an international expert panel of the European Society for Blood and Marrow Transplantation (EBMT) regarding the use of HSCT in inflammatory rheumatic diseases. These recommendations include detailed information on the indications, contraindications and warning signals for disease and comprehensive recommendations for diagnostic evaluation and monitoring. They are intended to guide rheumatologists in identifying suitable patients and providing interdisciplinary care.