Systemic lupus erythematosus (SLE) is a classic systemic autoimmune disease. Standard treatment consists of chronic therapy with antimalarials, glucocorticoids and immunosuppressive/cytotoxic drugs, which is associated with considerable side effects. In contrast, immunoablation of autoreactive immunologic memory followed by autologous stem cell transplantation (ASCT) has been the only regimen capable of inducing long-term remission of up to 10 years after cessation of immunosuppressive therapy, even in severely affected patients. Introduced in 1996, the procedure has since been performed in 147 patients with severe SLE refractory to standard treatment in clinical studies worldwide. Most of these patients achieved clinical long-term remission. However, SLE relapses and secondary autoimmune disorders have been reported. Transplant-related mortality occurred in 6% of the 147 cases, with a wide center effect (2-13%). Here we summarise the results published in the literature on immunoablation followed by ASCT in SLE and discuss future perspectives for optimising this therapeutic approach. It may be possible to improve the outcome and reduce the risks of treatment by identifying patients with a poor prognosis at an early stage, before irreversible organ damage has taken place.