Mesenchymal stem/stromal cells (MSCs) are commonly used as a source of cellular therapy due to their strong immunosuppressive and regenerative effects. One of the key mechanisms of MSC efficacy appears to derive from their paracrine activity. Recently, it has been shown that the secretion of different factors through extracellular vesicles known as exosomes, orchestrate the principle mechanisms of action of MSCs after infusion. The use of MSC-derived exosomes may provide considerable advantages over their counterpart live cells, potentially reducing undesirable side effects including infusional toxicities. In this review, we examine clinical trials of MSC-derived exosomes currently in progress for gene delivery, regenerative medicine, and immunomodulation. In addition, we summarize the limitations and clinical potential of this cell-free therapeutic strategy.