Exosomes, containing molecular constituents of their cell of origin, including proteins and nucleic acids, were first discovered in immature red blood cells in 1983. Excellent intercell communication can be achieved by shuttling these various molecules between cells. Stem cell-derived exosomes (SC-Exos) contain paracrine-soluble factors that play important roles in tissue development, homeostasis, and regeneration. This paracrine activity of SC-Exos has been found to be a predominant mechanism by which stem cell-based therapies mediate their effects on degenerative, autoimmune and/or inflammatory diseases. Compared to other types of stem cells, human embryonic stem cells (hESCs), human induced pluripotent stem cells (hiPSCs), human mesenchymal stem cells (hMSCs) are the most popular because of their efficient immunomodulatory effects. The advantages and disadvantages of using exosomes isolated from the stem cell trio for therapeutic applications are further discussed in this review.