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Autologous haematopoietic stem cell transplantation (aHSCT) is commonly used for the treatment of haematological cancers, but is increasingly used in the treatment of patients severely affected by autoimmune diseases (ADs). In fact, ADs have become the fastest growing indication for aHSCT. A wide range of diseases have been treated, but the field has focused on three areas: multiple sclerosis, diffuse cutaneous systemic sclerosis and Crohn's disease, where there are populations of patients for whom disease control remains unsatisfactory despite the advent of biological and targeted small molecule therapies. Scientific studies of immune reconstitution have provided support for a ‘rebooting’ of the immune system through a re-diversification of naive and regulatory immune effector cells. In addition, there may be health economic benefits from a single one-off procedure. Even so, the treatment with aHSCT is intensive with a range of toxicities and risks which, despite being routine to transplant haematologists, are less familiar to disease specialists. Close collaboration between transplant haematologists and relevant disease specialists in patient selection, clinical management and follow-up is mandatory. Ideally, patients should be treated on a clinical trial if available.