Cell-based therapies bear promise as a means to dampen autoaggressive immune reactions and induce tolerance in patients with severe rheumatic autoimmune diseases. Of the various types of cell-based therapies, immunoablative treatment combined with autologous hematopoietic stem cell transplantation has been used in more than 1000 patients with severe autoimmune diseases worldwide, including patients with rheumatoid arthritis, juvenile idiopathic arthritis, systemic lupus erythematosus, and systemic sclerosis. Long-term improvements of disease activity have been documented, albeit at the expense of treatment-related toxicity and mortality. Based on the results of pilot studies, prospective randomized controlled trials have been initiated to compare safety and efficacy of hematopoietic stem cell transplantation versus conventional treatment. Therapies involving mesenchymal stromal cells are currently being explored in clinical settings because of their anti-inflammatory and tissue regenerative properties and their favorable risk/benefit ratio.