tMSCs are an extensively used cell type in clinical trials today. The initial rationale for their clinical test-ing was based on their differentiation potential. However, the lack of correlation between functionalimprovement and cell engraftment or differentiation at the site of injury has led to the proposal thatMSCs exert their effects not through their differentiation potential but through their secreted product,more specifically, exosomes, a type of extracellular vesicle. We propose here that MSC exosomes func-tion as an extension of MSC’s biological role as tissue stromal support cells. Like their cell source, MSCexosomes help maintain tissue homeostasis for optimal tissue function. They target housekeeping biolog-ical processes that operate ubiquitously in all tissues and are critical in maintaining tissue homeostasis,enabling cells to recover critical cellular functions and begin repair and regeneration. This hypothesisprovides a rationale for the therapeutic efficacy of MSCs and their secreted exosomes in a wide spectrumof diseases. Here, we give a brief introduction of the biogenesis of MSC exosomes, review their physiolog-ical functions and highlight some of their biochemical potential to illustrate how MSC exosomes couldrestore tissue homeostasis leading to tissue recovery and repair.