PURPOSE OF REVIEW: Autologous hematopoietic stem cell transplantation (HSCT) is a promising therapeutic modality for severe autoimmune diseases. In this review, we will outline the immunological mechanisms and the clinical evidence and experiences for therapeutic HSCT in autoimmune diseases, with particular focus on systemic sclerosis (SSc) and multiple sclerosis (MS). RECENT FINDINGS: Approximately 3000 patients with autoimmune diseases worldwide have been treated with HSCT. HSCT in SSc has been shown in three randomized controlled trials to be associated with significant long-term event-free survival despite some transplant-related mortality in the first year. A recent controlled trial in MS has also show benefit with transplant. SUMMARY: The aim of HSCT is to ‘reset’ one’s immune system into a naïve and self-tolerant state through immune depletion and regulation. HSCT requires careful patient selection, close collaboration between physicians and expertise of transplant team to ensure optimal outcome.