2018 was the year of the first marketing authorization of an allogeneic stem cell therapy by the European Medicines Agency. The authorization concerns the use of allogeneic adipose tissue derived mesenchymal stromal cells (MSCs) for treatment of complex perianal fistulas in Crohn's disease. This is a breakthrough in the field of MSC therapy. The last few years have furthermore seen some breakthroughs in the investigations to the mechanisms of action of MSC therapy. Although the therapeutic effects of MSCs have largely been attributed to their secretion of immunomodulatory and regenerative factors, it has now become clear that some of the effects are mediated through host phagocytic cells that clear administered MSCs and in the process adapt an immunoregulatory and regeneration supporting function. The increased interest in therapeutic use of MSCs and the ongoing elucidation of the mechanisms of action of MSCs are promising indicators that 2019 may be the dawn of the therapeutic era of MSCs and that there will be revived interest in research to more efficient, practical, and sustainable MSC-based therapies. Stem Cells Translational Medicine2019.