Stem cell therapy has developed extensively in recent years, leading to several new clinical fields. The use of mesenchymal stromal cells sparks special interest, as it reveals the importance of the paracrine and immunomodulatory effects of these supporting cells, in disease and in cure. This review discusses our current understanding of the basic clinical principles of stem cell therapy and demonstrates the broad range of this treatment modality by examining two relatively new therapeutic niches – autoimmune and cardiac diseases.